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BJU International 2000 86 (6), 754

POINT OF TECHNIQUE
Effects of botulinum A toxin on detrusor-sphincter dyssynergia in patients with multiple sclerosis
Y. Akkoç (1), Y. KiRazli (1), C. Özyurt*, E. IdiMan† and R. AksiT(1)
(1) Departments of Physical Medicine and
(2) Rehabilitation, and *Urology, Medical Faculty of Ege University, and
(†) Department of Neurology, Medical Faculty of Dokuz Eylul University, Bornova, Izmir, Turkey

Indications

Bladder problems are a significant cause of morbidity in patients with multiple sclerosis (MS) [1]. Bladder symptoms in these patients usually arise as a result of the interruption of the pathways between the sacral cord and pons, which may lead to detrusor hyper-reflexia and detrusor-sphincter dyssynergia (DSD), defined as an involuntary contraction of the external urethral sphincter during detrusor contraction [2]. The reported incidence of DSD in patients with MS is 18–66% [1, 3–7]. Because DSD in these patients may force reflux of urine into the ureters, upper urinary tract damage, e.g. pyelonephritis and hydronephrosis, may develop in the presence of UTI [8].

The aim of treatment for a patient with DSD is to reduce the urethral resistance and thus improve voiding [1]. CISC, a well established technique, is the treatment of choice in patients with MS and disorders of bladder emptying [7]. The management of patients who are unable to perform CISC is difficult. They can either use a long-term indwelling bladder catheter or undergo surgery; the results of the latter are generally unsatisfactory [9,10]. Striated muscle relaxants such as baclofen, diazepam and dantrolene have also been used, but these may increase general fatigue and muscle weakness [11].

Several investigators have reported good results using transurethral or transperineal injections with botulinum-A toxin (BTX-A) for the treatment of DSD in patients with spinal cord injury (SCI) [12–17]. Whether DSD in MS responds to this treatment as it does in SCI is currently unknown. Thus, we evaluated the efficacy of transurethral BTX-A injections in three patients with MS and DSD.

Methods

Indications  Comparison with other methods  Disadvantages  References  Authors
Three patients with MS and DSD received transurethral injections with BTX-A. Before entering the study a complete medical history was taken and the patients were examined physically. The severity of disease was assessed by Kurtzke's expanded disability status scale (EDSS) [18]; the patients' characteristics are shown in Table 1. All three patients had complained of urge incontinence, interrupted urinary stream, nocturnal enuresis and incomplete bladder emptying. Two of the patients could void spontaneously but with high postvoid residual urine volumes (PVRs). They had refused CISC because they found it difficult to use. The third patient had used CISC for the previous 6 months but was then unable to continue, having recently developed further upper limb disability, and had begun to use an indwelling catheter.
 
 

Table 1  The patients' characteristics, and the urodynamic values before and after treatment

Characteristic/variable	Patient
	1	2	3
Age (years)
At study	50	33	35
At start of MS	32	17	30
At start of urinary trouble	45	30	33
EDSS score	6.5	6.5	8.0
Urodynamics (before/1 month after treatment)
Max. urethral pressure (cmH2O)	105/88	65/54	120/105
Max. detrusor pressure (cmH2O)	70/37	53/41	98/75
Functional capacity (mL)	250/370	237/365	120/175
PVR (mL)	200/80	175/70	220/120

The patients were given full information and all agreed to be treated with transurethral BTX-A injections; a consent form was signed by all patients. Before the urodynamic studies, UTI was excluded by negative cultures of urine samples, obtained by sterile catheterization of the bladder. Urodynamic studies were obtained at baseline using a Dantec Duet™ urodynamics unit (Dantec Medical, Skovlunde, Denmark); in all patients DSD was confirmed as responsible for the urinary symptoms. Cystometrography with EMG, urethral pressure profile and measurement of PVR was repeated 1 month after the BTX-A injections. Every 2 weeks the PVR was measured and the patients were evaluated clinically.

Each patient received four transurethral injections of 25 IU of BTX-A (Botox, Allergan Inc., Irvine, CA; diluted in 1 mL normal saline with no preservative) into the external urethral sphincter between the 3 and 9 o'clock or 9 and 3 o'clock positions, delivered through a cystoscope with a special injection needle.

There was a clinical improvement »15 days after the injection in all three patients. Urinary incontinence was completely abolished in two of those who had had urinary leakage 2–4 times during the day and once to twice during the night before treatment. These two patients were able to void spontaneously before treatment, but with high PVRs. After treatment the PVR decreased considerably (Table 1). The third patient had urinary incontinence 4–5 times during the day and once or twice during the night when she was using CISC, before the indwelling catheter was placed. After treatment the frequency of urinary leakage decreased to once to twice during the day and to once every other night. After the BTX-A injections, her PVR was significantly lower (Table 1).

The good clinical response persisted for »3 months in all patients; although all had had frequent UTIs previously, no UTI occurred during this period. The PVR measured after 3 months was higher than the previous measurements, but remained lower than the baseline PVR by a mean of 25 mL.

A urodynamic study after 1 month showed an increase in the functional detrusor capacity by a mean of 49% and a decrease in the maximal detrusor pressure during voiding by 31%. The maximum urethral pressure and PVR were decreased by 15% and 55%, respectively (Table 1). No side-effects, e.g. nausea, vomiting, dry mouth, dysphagia or weakness of the muscles, occurred.

Comparison with other methods

Repeated courses of BTX-A injection seem to have a longer duration of effectiveness than a single course. Schurch et al.[14] used different protocols in their study and concluded that one injection of BTX-A improved vesico-urethral function for only 2–3 months, whereas the effect of three repeated injections once a month lasted 9–13 months. The present study using one injection of BTX-A into the external urethral sphincter suggests that injections should be repeated every 3 months.

DSD is common in patients with MS and may result in significant impairment [1]; in such patients, urological complications, e.g. repeated episodes of urosepsis, VUR and urolithiasis, have been reported to show a high correlation with the presence of DSD [19]. CISC is the treatment of choice in these patients [8] but is clearly impossible when the patient has neurological involvement of their upper limbs; they are then usually chair-bound and cannot transfer to the toilet. One of the present patients was chair-bound and the rest were able to walk with a frame, but the two patients who had adequate manual dexterity were unwilling to use CISC. Although a long-term indwelling catheter can be considered, it causes many problems and should generally be regarded as a temporary measure [20].

There is a need for alternative treatments for patients with MS and DSD who are unable or unwilling to use CISC and who do not accept surgical procedures. In the present study, after transurethral injections with 100 IU of BTX-A, the urodynamic evaluation showed an increase in functional detrusor capacity, a decrease in maximal detrusor pressure during voiding, maximal urethral pressure and PVR. The dose of 100 IU of BTX-A seems to be adequate for DSD [14, 16]. In accordance with the improved urodynamic variables there was also a clinical improvement; frequent UTIs, a significant problem before BTX-A injection, did not recur during the 3 months after injection.

Disadvantages

The management of DSD with BTX-A is expensive, as re-injections at 3-month intervals are required. Thus the cost-effectiveness of BTX-A should be investigated and balanced against that of surgical procedures. Studies with more patients will help to clarify the effectiveness of such treatment in these patients, especially in the long-term.

References

Indications  Methods  Comparison with other methods  Disadvantages  Authors

1 Gallien P, Robineau S, Nicolas B, Le Bot MP, Brissot R, Verin M. Vesicourethral dysfunction and urodynamic findings in multiple sclerosis: a study of 149 cases. Arch Phys Med Rehabil 1998; 79: 255–7

2 Andersen JT & Bradley WE. The syndrome of detrusor-sphincter dyssynergia. J Urol 1976; 116: 493–5

3 Weinstein MS, Cardenas DD, O'Shaughnessy EJ, Catanzaro ML. Carbon dioxide cystometry and postural changes in patients with multiple sclerosis. Arch Phys Med Rehabil 1988; 69: 923–7

4 Barbalias GA, Nikiforidis G, Liatsikos EN. Vesicourethral dysfunction associated with multiple sclerosis: clinical and urodynamic perspectives. J Urol 1998; 106: 106–11

5 Giannantoni A, Scivoletto G, Di Stasi SM et al. Lower urinary tract dysfunction and disability status in patients with multiple sclerosis. Arch Phys Med Rehabil 1999; 80: 437–41

6 McGuire EJ & Savastano JA. Urodynamic findings and long-term outcome management of patients with multiple sclerosis-induced lower urinary tract dysfunction. J Urol 1984; 132: 713–5

7 Blaivas JG, Holland NJ, Giesser B, LaRocca N, Madonna M, Scheinberg L. Multiple sclerosis bladder. Studies and care. Ann NY Acad Sci 1984; 436: 328–46

8 Holland N. Bladder management in multiple sclerosis. MS Management 1994; 1: 7–11

9 Vapnek JM, Couillard DR, Stone AR. Is sphincterotomy the best management of the spinal cord injured bladder ? J Urol 1994; 151: 961–4

10 Lockhard JL, Vorstman B, Weinstein D, Politano VA. Sphincterotomy failure in neurogenic bladder disease. J Urol 1986; 135: 86–9

11 Fowler CJ, van Kerrebroeck PE, Nordenbo A, Van Poppel H. Treatment of lower urinary tract dysfunction in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 1992; 55: 986–9

12 Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 1988; 139: 919–22

13 Dykstra DD & Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil 1990; 71: 24–6

14 Schurch B, Hauri D, Rodic B, Curt A, Meyer M, Rossier AB. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients. J Urol 1996; 155: 1023–9

15 Schurch B, Hodler J, Rodic B. Botulinum A toxin as a treatment of detrusor-sphincter dyssynergia in patients with spinal cord injury: MRI controlled transperineal injections. J Neurol Neurosurg Psychiatry 1997; 63: 474–6

16 Gallien P, Robineau S, Verin M, Le Bot MP, Nicolas B, Brissot R. Treatment of detrusor sphincter dyssynergia by transperineal injection of botulinum toxin. Arch Phys Med Rehabil 1998; 79: 715–7

17 Wheeler Js Jr, Walter JS, Chintam RS, Rao S. Botulinum toxin injections for voiding dysfunction following SCI. J Spinal Cord Med 1998; 21: 227–9

18 Kurtzke JF. Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52

19 Blaivas JG & Barbalias GA. Detrusor external sphincter dyssynergia in men with multiple sclerosis: an onimous urologic condition. J Urol 1984; 131: 91–4

20 Fowler CJ. Bladder dysfunction in multiple sclerosis: causes and treatment. Int MS J 1994; 1: 99–107

Authors

Y. Akkoç, MD, Specialist.
Y. Kirazli, MD, Professor.
C. Özyurt, MD, Associate Professor.
E. Idiman, MD, Professor.
R. Aksit, MD, Professor.

Correspondence:
Y. Akkoc, Ege Universitesi Tip Fakultesi, Fiziksel Tip ve Rehabilitasyon Anabilim Dali, Bornova, Izmir, Turkey
e-mail: akkocn@hotmail.com
 

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