Uro-neurology Group

Summary

The department of Uro-Neurology was first set up in 1987 – so called because its aim was to take a neurological approach to bladder problems. Elsewhere an interest in neurological bladder problems had been lead by urologists so that most other specialist centres are called “Neuro-Urology Departments”. There are now a few other “Uro-Neurology” departments in the world and the subject of the neurological control of pelvic organ function is now recognised to be one of great clinical importance.

Originally providing a service predominantly for bladder problems of neurological patients at The National Hospital, the referral base has gradually expanded and the department now receives referrals from gynaecologists, urologists, neurologists, and andrologists UK wide.

In additional to the clinical service the department offers, research has been a major focus. Several important new therapies have become available in the last 10 years and research in the department has included the investigation of new treatments and their mechanism of action.

Prof Fowler was joined by part time consultants Uro-gynaecolgist Ms Elneil in 2006 and last year by Urologist, Mr Rizwan Hamid. The department now has 3 nurses, two of whom are clinical nurse specialist continence advisors. There are 2 clinical fellows and we have had a succession of visiting research fellows from Europe.

Current Projects

The effect of detrusor injection of botulinum toxin, a treatment introduced in Switzerland in 1999, is now recognised throughout the world as being a highly effective treatment for severe detrusor overactivity. At Queen Square the technique for giving this as a minimally invasive outpatient treatment was developed and this has been successfully used to treat patients since 2002. Still unlicensed this was used to treat patients first as a research project, but subsequently with permission of the Use of Medicines Committee at UCLH. Patients experience a relief from urinary urgency and urgency incontinence for between 9-12 months and repeated injections have proved particularly suitable for patients with Multiple Sclerosis. So far the main use of this treatment has been for patients with neurogenic detrusor overactivity of spinal rather than cerebral origin and the majority of such patients usually have a co-existent impairment of voiding. Following detrusor injections of botulinum toxin, the majority of patients have to do clean intermittent self-catherisation but despite this, an improvement in the QoL can be documented following sequential injections (see Figure 1). In the last 10 years the department has published a number of papers on the beneficial effect of detrusor injections of botulinum toxin (see a selected publication list for the last 3 years below)

In 2006 a publication from Uro-Neurology speculated on the complex mechanism of action of this treatment. Figure 2 is a summary cartoon illustrating the various concepts described in the paper. (This paper is currently the most highly cited publication in European Urology on a topic which is not related to urological cancer). Its mechanism of action is still not fully understood and we are embarking on further study of this, taking bladder biopsies from patients before and after treatment. This work is part of a European collaboration funded by an FP7 grant Incomb.

Non-surgical urinary retention is a problem for which many patients are referred, and although approximately 25% of the women are identified as having the syndrome described by Prof Fowler in 1989, research continues to try and identify significant other factors in remaining these patients. Recent data suggests that opiates may be a factor in some and may compound the problem in Fowler’s syndrome so that patients with that disorder who take opiates are particularly likely to develop urinary retention.

Sacral neuromodulation continues to be an effective treatment in restoring voiding in women with Fowler’s syndrome and the department has played an important part in establishing the mechanism of action of that intervention. It has long been a conundrum as to how sacral neuromodulation could be effective in treating symptoms of an overactive bladder and urinary retention but our research has shown that it is probably by “reinforming” the pontine micturition centre that the ability to void is restored (Figure 3). The sphincter abnormality appears to be unaffected.

Ms Elneil, consultant uro-gynaecologist, is now expanding the indications to include patients with urgency incontinence, mixed urinary incontinence, and mixed urinary and faecal incontinence. Dr Emmanuel is looking at the effects of sacral neuromodulation in bowel disorders, both intractable constipation and incontinence. A longer term study of the bowel dysfunction experienced by patients with MS has been running for the last year. The aim is to identify the physiological phenotypes of gut dysfunction and if possible identify their differing aetiologies. The ultimate aim is to target therapy specifically, for this otherwise difficult to treat group. A similar study on spinal injury has been ongoing for longer, with publications and targets emerged, the latter the subject of further trials. Ms Elneil is also going to examine the effect of pudendal nerve stimulation for voiding disorders refractory to sacral neuromodulation.

The effect of Botulinum toxin injection into the striated urethral sphincter in women with a primary disorder of sphincter relaxation (Fowler’s syndrome) is currently being investigated, both in those with complete urinary retention and those with obstructed voiding.

Information for Patients

Prof Fowler receives referrals through Choose and Book as well as GP or consultant to consultant referrals. Ms Elneil, Dr Emmanuel and Mr Hamid also run weekly outpatients to which patients can be referred by their GPs or other hospital consultants with PCT approval.

Please also see our webpage on Fowler's Syndrome

Research Team

Prof Clare Fowler

Ms Sohier Elneil

Dr Anton Emmanuel

Mr Rizwan Hamid

Dr Jalesh Panicker

Dr Catherine Dalton

Mr Shahid Khan

Dr Xavier Game

Dr Giuseppi Preziosi

Mrs Collette Haslam

Ms Gwen Gonzales

Mrs Juliana Ochalur

Teaching Activity

Staff from Uro-Neurology contribute to teaching for neurologists, urologist and gynaecologists at UCL run courses, as well as national courses organized by professional training organizations and industry sponsored events. Nurses from the department are involved in teaching on their professional training courses too.

Over the course of the last year members of the department have been busy writing chapters for a book “Pelvic Organ Dysfunction in Neurological Disease”. This has been edited by Prof Fowler, Dr Jalesh Panicker and Dr Anton Emmanuel and consists of 19 chapters, all written by healthcare professionals who have worked in Uro-Neurology in recent years. The book is to be published by Cambridge University Press and a symposium with the same title is planned for this summer. All the speakers are contributors to the book.

Selected Publications from the last 3 years

1. Kalsi, V., G. Gonzales, Popat, R., Apostolidis, A, Elneil, S., Dasgupta, P., Fowler, C. J.et al. (2007). "Botulinum injections for the treatment of bladder symptoms of multiple sclerosis." Ann Neurol 62(5): 452-7.

2. van Kerrebroeck, P. E., A. C. van Voskuilen, Heesakkers, J. P., Lycklama a Nijholt, A. A, Siegel, S,Jonas, U.,Fowler, C. J, Fall, M.,Gajewski, J. B. Hassouna, M. M.,Cappellano, F., Elhilali, M. M., Milam, D. F, Das, A. K., Dijkema, H. E. and van den Hombergh, U. (2007). "Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study." J Urol 178(5): 2029-34.

3. Apostolidis, A., R. Popat, Harper, M., Fowler, C. J and Dasgupta, P (2007). "Successful treatment with botulinum toxin A after failed augmentation ileocystoplasty." Nat Clin Pract Urol 4(5): 280-4.

4. DasGupta, R., R. B. Kavia, and Fowler, C. J. (2007). "Cerebral mechanisms and voiding function." BJU Int 99(4): 731-4.

5. Rees, BM., Clare J. Fowler, C.P. Maas (2007) "Sexual Function in Men and Women with Neurological Disorders" Lancet, 369(9560):512-25.

6. Datta, S. N., C. Chaliha, Singh, A., Gonzales, G., Mishra, V. C., Kavia, R. B., Kitchen, N., Fowler, C. J., Elneil, S. . (2008). "Sacral neurostimulation for urinary retention: 10-year experience from one UK centre." BJU Int 101(2): 192-6.

7. Apostolidis A, Fowler CJ. The use of botulinum neurotoxin type A (BoNTA) in urology. J Neural Transm. 2008. Fowler, C.J., D. Griffiths, and W.C. de Groat, The neural control of micturition. Nature Reviews Neuroscience, 2008. 9(6): p. 453-66.

8. Fowler, C.J., Editorial Comment on: Influence of Nerve Transsections and Combined Bladder Filling on Intravesical Electrostimulation-Induced Bladder Contraction in the Rat. Eur Urol, 2008.

9. Chancellor MB, Fowler CJ, Apostolidis A, de Groat WC, Smith CP, Somogyi GT, Roger Aoki K (2008) Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol, 6,5, 319-28

10. Apostolidis A, Jacques TS, Freeman A, Kalsi V, Popat R, Gonzales G, Datta SN, Ghazi-Noori S, Elneil S, Dasgupta P, Fowler CJ (2008) Histological Changes in the Urothelium and Suburothelium of Human Overactive Bladder following Intradetrusor Injections of Botulinum Neurotoxin Type A for the Treatment of Neurogenic or Idiopathic Detrusor Overactivity. Eur Urol, 53, 1245-1253

11. Kalsi V, Apostolidis A, Gonzales G, Elneil S, Dasgupta P, Fowler CJ (2008) Early Effect on the Overactive Bladder Symptoms following Botulinum Neurotoxin Type A Injections for Detrusor Overactivity. Eur Urol 54:181-187

12. Gilman S, Wenning GK Low PA, Brooks Dj, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology;71:670-676.

13. Apostolidis A, Dasgupta P, Denys P, Elneil S, Fowler CJ, Giannantoni A, Karsenty G, Schulte-Baukloh H, Schurch B, Wyndaele J-J. (2009) Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol;55, 100-120.

14. Kessler TM, Khan S, Panicker J, Roosen A, Elneil S, Fowler CJ (2009) Clean intermittent self-catheterization after botulinum neurotoxin type A injections: short-term effect on quality of life. Obstet Gynecol 113:1046-1051

15. Fowler CJ, Panicker JN, Drake M, Harris C, Harrison SC, Kirby M, Lucas M, Macleod N, Mangnall J, North A, Porter B, Reid S, Russell N, Watkiss K, Wells M (2009) A UK consensus on the management of the bladder in multiple sclerosis. J Neurol Neurosurg Psychiatry 80:470-477

16. Kessler TM, Fowler CJ, Panicker JN (2009) Sexual dysfunction in multiple sclerosis. Expert Rev Neurother 9:341-350

17. Khan S, Kessler TM, Apostolidis A, Kalsi V, Panicker J, Roosen A, Gonzales G, Haslam C, Elneil S, Fowler CJ, Dasgupta P (2009) What a patient with refractory idiopathic detrusor overactivity should know about botulinum neurotoxin type a injection. J Urol 181:1773-1778

18. Sahai A, Sangster P, Kalsi V, Khan MS, Fowler CJ, Dasgupta P (2009) Assessment of urodynamic and detrusor contractility variables in patients with overactive bladder syndrome treated with botulinum toxin-A: is incomplete bladder emptying predictable? BJU Int 103:630-634

19. Roth B, Studer UE, Fowler CJ, Kessler TM (2009) Benign prostatic obstruction and parkinson's disease--should transurethral resection of the prostate be avoided? J Urol 181:2209-2213

20. Roosen A, Apostolidis A, Elneil S, Khan S, Panicker J, Brandner S, et al. Cadherin-11 up-regulation in overactive bladder suburothelial myofibroblasts. J Urol. 2009 Jul;182(1):190-5.

21. Khan S, Panicker J, Roosen A, Gonzales G, Elneil S, Dasgupta P, et al. Complete Continence after Botulinum Neurotoxin Type A Injections for Refractory Idiopathic Detrusor Overactivity Incontinence: Patient-Reported Outcome at 4 Weeks. Eur Urol. 2009 Apr 21.

22. Kessler TM, Khan S, Panicker J, Roosen A, Elneil S, Fowler CJ. Clean intermittent self-catheterization after botulinum neurotoxin type A injections: short-term effect on quality of life. Obstet Gynecol. 2009 May;113(5):1046-51.

23. .Roosen A, Datta SN, Chowdhury RA, Patel PM, Kalsi V, Elneil S, et al. Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment. Eur Urol. 2009 Jun;55(6):1440-8.

24. .Drake MJ, Fowler CJ, Griffiths D, Mayer E, Paton JF, Birder L. Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanisms. Neurourol Urodyn. 2010, 29(1):119-27.

25. .Fowler CJ, Griffiths DJ. A decade of functional brain imaging applied to bladder control. Neurourol Urodyn., 2010 ,29(1):49-55.

26. Kavia, R., R. Dasgupta, et al. (2010). "A functional magnetic resonance imaging study of the effect of sacral neuromodulation on brain responses in women with Fowler's syndrome." BJU Int 105(3): 366-72.

27. Preziosi G, Emmanuel A. Neurogenic bowel dysfunction: pathophysiology, clinical manifestations and treatment. Expert Rev Gastroenterol Hepatol. 2009 Aug;3(4):417-23

28. Emmanuel,A.V., Chung,E.A., Kamm,M.A., Middleton,F. (2009). Relationship between gut-specific autonomic testing and bowel dysfunction in spinal cord injury patients. Spinal Cord 47(8), 623-627.

29. Chung,E.A., Emmanuel,A.V. (2006). Gastrointestinal symptoms related to autonomic dysfunction following spinal cord injury. Progress in Brain Research 152, 317-333.

30. Craggs,M.D., Balasubramaniam,A.V., Chung,E.A.L., Emmanuel,A.V. (2006). Aberrant reflexes and function of the pelvic organs following spinal injury in man. Auton Neurosci 126-127, 355-370.

Chapters in Books

1. Kalsi, V., Elneil, S and Fowler Clare J. (2008). Physiology of the urogenital system in Urogenital Pain in Clinical Practice, Ed Andrew P. Baranowski, Paul Abrams, Magnus Fall, Chapter 4, 45-55.

2. Podnar Simon and Fowler Clare (2008) The application of electrodiagnostic methods to investigate female pelvic organ dysfunction: Chapter 11. In Female Urology, 3rd Edition, eds Schlomo Raz & Larissa V. Rodriguez

3. Kalsi, V, Fowler CJ. (2008) Bladder and sexual dysfunction in multiple sclerosis. In CS Raine, HF McFarland, R Hohlfeld (Eds) Multiple Sclerosis. A Comprehensive Text. Saunders Elsevier, pp. 391-400.

4. .Sakakibara, R, Fowler, Clare J. and Hattori, Takamichi Urinary dysfunction in multiple system atrophy, Ryuji Chapter 22, 282-293 The textbook of the Neurogenic Bladder 2nd Edition 2008 Informa Healthcare, UK ISBN-13: 978 0 415 423168 Edited by Jacques Corcos and Erik Schick

5. Podnar, S and Fowler, Clare J.Electrophysiologic evaluation: basic principles and clinical applications, Chapter 43 p511-529, The textbook of the Neurogenic Bladder 2nd Edition 2008 Informa Healthcare, UK ISBN-13: 978 0 415 423168 Edited by Jacques Corcos and Erik Schick

6. Apostolos Apostolidis and Clare J. Fowler (2009). Neurophysiology of Micturition: What's New? in Continence - Current Concepts and Treatment Strategies eds Gopal H. Badlani, G. Willy Davila, Martin C. Michel, Jean J.M.C.H. de la Rosette . Chapter 2, 17-33.

7. Clare J. Fowler and David B. Vodusek (2009). Electrophysiology in Pelvic Floor Re-education, Principles and Practice, 2nd Edition , eds Kaven Baessler, Bernard Schussler, Kathryn L. Burgio, Kate H. Moore, Peggy A. Norton, Stuart L. Stanton. Chapter 2.8, 155-161.

8. Clare J.Fowler and Ryuji Sakakibara (2009) "Bladder dysfunction in Parkinson's disease" in Non-Motor Symptoms of Parkinson's Disease edited by K.Ray Chaudhuri, E.Toosa, A. Schapira and W. Poewe, Oxford University Press. Chapter 17 pp215-224.

Quality of life questionaires UDI-6, IIQ-7 and EQ-5D are available online

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Quality of life scores UDI -6 (Urogenital Distress Inventory -6) and IIQ -7 (Incontinence Impact Questionnaire -7) pre and post BoNT-A.

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Page last modified on 13 may 13 17:38