Botulinum Toxin injection to the sphincter

For detailed introductory information, please refer to this.

1. Concept

  • By injection of botulinum neurotoxin into the external urethral sphincter, gradual paralysis of striated sphincter activity can be induced to prevent dangerous upper urinary tract damage due to DSD, and to improve spontaneous voiding in some limited circumstances.
  • For more information, please refer to this

2. History

  • In 1988, Dykstra first described the use of botulinum toxin type A in 11 men with SCI and DSD [Dykstra 1988].

3. Purpose of this procedure

  • To decrease outlet resistance and facilitate voiding dysfunction.
  • In some cases where CIC is impeded at the striated sphincter, which reflexly contracts when contacted by the catheter, botulinum toxin injection will resolve the problem and prevent urethra false passage development.

4. Indication

5. Procedure

(1) Tansperineal injections (percutaneous)

  • transperineally under EMG control [Schurch 1997]
  • Does not require general anesthesia, catheterization, or prophylactic treatment of AD [Petit 1998]

(2) Cystoscopic techniques

  • Cystoscopic techniques [Schurch 2000]
  • Little significant difference in the efficacy between the transperineal and transurethral approaches. [Schurch 1997]

6. Clinical Outcomes

Author

Subjects and Methods

Results

Comments

Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD.[ J Urol. 1988]

Botulinum toxin type A

11 SCI men with DESD

Successful denervation of the sphincter, as demonstrated by EMG urethral pressure profile decreased by an average of 27 cm H2O and the postvoid residual urine volumes decreased by an average of 146 mL.

Effects of therapy lasted an average of 50 days, and AD was apparently reduced in 5 patients.

Dykstra DD, Sidi AA. [Arch Phys Med Rehabil. 1990]

Double-blind study

Botulinum toxin type A versus saline

5 SCI men with DESD

 

Urethral pressure profiles decreased an average of 25 cm H2O, postvoid residual urine volumes decreased to an average of 125 mL, and bladder pressure decreased to an average of 30 cm H2O during voiding. In contrast, the 2 men receiving saline injections experienced no such change

 

Petit H, Wiart L, Gaujard E, Le Breton F, Ferriere JM, Lagueny A, Joseph PA, Barat M. [Spinal Cord. 1998]

Botulinum toxin type A

17 SCI/D patients

The postvoid residual urine volumes decreased by an average of 176 mL, bladder voiding pressure decreased by 19 cm H2O, and urethral pressure decreased by 24 cm H2O.

The effects of therapy lasted around 2 to 3 months.

Dose of botulinum toxin type A was significantly lower than that used by Dykstra and Sidi.

Schurch B, Hauri D, Rodic B, Curt A, Meyer M, Rossier AB. [J Urol. 1996]

Botulinum toxin type A

24 SCI patients with DESD

21 showed improvement in urodynamic parameters and complete disappearance of DESD was observed in 8 patients
 
Only 9 patients in their study achieved lower postvoid residual urine volumes after treatment.

The patients who did not achieve lower postvoid residual urine volumes had prominent bladder neck dyssynergia or detrusor hypoactivity. Patients with DESD and bladder neck dyssynergia who were treated with botulinum toxin type A eventually showed a decrease in postvoid residual urine volumes after additional treatment with alpha-blockers.

Schurch B, Hodler J, Rodic B. [J Neurol Neurosurg Psychiatry. 1997]

3 different treatment regimes (100 U Botox injected once and possibly repeated 1 to 3 months; 100 U Botox injected monthly for 3 months and repeated after 6 to 12 months; and 250 U Dysport injected monthly for 3 months and repeated after 6 to 12 months)

 

Duration of action of monthly injections of 100 U for 3 months to be superior to one injection of 100 U (2 to 3 months versus 9 to 12 months).

 

7. Advantages

  • Systemic side effects can occur.
  • However, generalized weakness due to the toxins spreading in the blood is very rare.
  • For more information, please refer to this.

8. Disadvantages

  • Provide only temporary relief, and repeat injections are necessary every 3 to 8 months.
  • Factors that limit the success include bladder neck dyssynergia and poor bladder contractility [Petit 1998; Schurch 1996]
  • The factors cited may amount to the same thing: poor detrusor contractility is common in cervical lesions, and successful eradication of external sphincter activity may result in loss of the detrusor response to obstruction responsible for the high pressures in the untreated situation. In this case failure of bladder neck opening may reflect lack of a detrusor contraction rather than true bladder neck – bladder dysynergia. Overt dysynergia between bladder and internal sphincter (bladder neck, or pre prostatic sphincter) does occur in patients with cervical injuries but is very rare, and only in the setting of very dramatic autonomic dysreflexia.
  • For more information, please refer to this.

9. Current significance

  • Neurourologists have not yet found the ideal treatment for urodynamically significant DSD in male patients [Wein 1998]

Summary

Effectiveness

Effective but rather short duration

Safety

Reasonable but entry into the blood stream may induce a syndrome of extreme weakness in rare cases (5 reported in the literature). Safer than sphincterotomy

Ease of application

Relatively easy 
intransurethral mode, but prevention of dysreflexia is required in high lesions.

Patient Comfort

N/A

Cost

Expensive material, but relatively inexpensive all together, if done in a clinic or ambulatory setting. Inexpesive when compared to sphincterotomy

10. Other Comments

  • Other trials: Yoshiyama [Yoshiyama 2000] described a laboratory use of i.v. α-bungarotoxin as improving voiding in SCI rats. The drug is a toxin extracted from the venom of a Formosan snake; it selectively blocks nicotinic receptors without influencing transmission in autonomic ganglia. Although a long way from clinical use, nicotinic receptors in the striated sphincter have been shown to be a potential target for drug therapy for DESD.
  • It is reported that botulinum toxin injection to the urethral sphincter decreased autonomic dysreflexia symptoms [Dykstra 1988].

Key Points of This Section

  • Botox can effective decrease and or eliminate striated sphincter activity but the effect is limited in duration.
  • There are cicumstances where this treatment is ideal.

References

  • 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 May;139(5):919-22.
  • Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990 Jan;71(1):24-6.
  • Petit H, Wiart L, Gaujard E, Le Breton F, Ferriere JM, Lagueny A, Joseph PA, Barat M. Botulinum A toxin treatment for detrusor-sphincter dyssynergia in spinal cord disease. Spinal Cord. 1998 Feb;36(2):91-4.
  • 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 Mar;155(3):1023-9. 
  • 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 Oct;63(4):474-6.
  • Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000 Sep;164(3 Pt 1):692-7.
  • Wein AJ. The role of external sphincterotomy for patients with a spinal cord lesion. J Urol. 1998 Sep;160(3 Pt 1):961.
  • Yoshiyama M, deGroat WC, Fraser MO. Influences of external urethral sphincter relaxation induced by alpha-bungarotoxin, a neuromuscular junction blocking agent, on voiding dysfunction in the rat with spinal cord injury. Urology. 2000 Jun;55(6):956-60.

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