resiniferatoxin and Spinal-Cord-Diseases

To investigate the therapeutic effect of resiniferatoxin in patients with chronic spinal cord lesions, as detrusor hyper-reflexia and external sphincter dyssynergia (DESD) are common phenomenon in such patients.. Twenty patients with chronic spinal cord lesions and DESD refractory to anticholinergic treatment were enrolled in a prospective study. They were treated with 30 mL of 10 micro mol/L resiniferatoxin for 30 min. Four types of response were recorded during instillation: type 1, a sustained high-pressure detrusor contraction followed by complete acontractility; type 2, a high-pressure contraction followed by progressively lower contractions; type 3, intermittent high-pressure detrusor contractions throughout the instillation; type 4, intermittent low-pressure detrusor contractions. The changes in clinical symptoms and urodynamics at baseline, during resiniferatoxin instillation and 1 month after treatment were compared.. All patients had DESD and 10 had autonomic dysreflexia; 18 had urinary incontinence and 13 had difficult urination. Continence and/or difficult urination improved in 12 patients, including all five with type 1, four with type 2, two with type 3 and only one with a type 4 response. Four patients became dry during the day and eight had less urgency and fewer incontinence episodes, and a significantly increased voided volume. Of the 13 patients who complained of difficult urination, eight had an improvement either by spontaneous voiding (five) or the Crede manoeuvre to voiding (three). The mean (sd) maximum cystometric capacity increased significantly after treatment, from 102.1 (31.5) to 236.6 (88.6) mL (P < 0.001), but the detrusor pressure showed no significant change, at 55.9 (23.2) to 47.5 (28.1) cmH2O. The external urethral sphincter showed intermittent activity during reflexic detrusor contractions at baseline.. Resiniferatoxin at 10 micro mol/L has a clinical effect on two-thirds of patients with a spinal cord lesion and detrusor hyper-reflexia, but not on the DESD. The initial response to resiniferatoxin instillation might predict a favourable therapeutic outcome.

Topics: Administration, Intravesical; Adult; Aged; Ataxia; Cholinergic Antagonists; Chronic Disease; Diterpenes; Drug Resistance; Female; Humans; Male; Middle Aged; Prospective Studies; Reflex, Abnormal; Spinal Cord Diseases; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination; Urodynamics

Resiniferatoxin (RTX), a substance isolated from some species of Euphorbia, a cactus-like plant, shows pharmacological effects similar to those of capsaicin. We have studied the possibility of treating detrusor hyperreflexia refractory to intravesical capsaicin in patients with chronic spinal cord injuries, thereby providing insight into the mechanism of action of RTX on sensory neurons and its possible future pharmacological and clinical use.. RTX saline solution (30 ml at a concentration of 10(-5) M) was instilled into the bladder of 7 patients with detrusor hyperreflexia, refractory to intravesical capsaicin therapy, and left in place for 30 min. Effects on bladder function were monitored during the treatment and at follow-up (15 days and 4 weeks later).. Fifteen days after RTX, the mean cystomanometric capacity increased significantly from 190 ml +/- 20 ml to 407.14 ml +/- 121.06 (p < 0.01), and it remained high four weeks later (421.66 +/- 74.40 p < 0.01). After 15 days, four patients had a pharmacologically induced detrusor areflexia. They emptied their bladders by clean intermittent catheterization. After four weeks, only two patients still had a pharmacologically induced detrusor areflexia. Clinically, three patients remained dry, and the other three reported a significant improvement in their incontinence and symptoms (frequency, urgency and nocturia).. By interfering with sensory unmyelinated fibers, intravesical RTX seems to be a promising treatment option for selected cases of detrusor hyperreflexia. The ideal dosage and treatment interval have not yet been established, and further studies are necessary to confirm our preliminary results.

Topics: Administration, Intravesical; Adult; Capsaicin; Diterpenes; Female; Humans; Male; Neurotoxins; Reflex, Abnormal; Spinal Cord Diseases; Time Factors; Urinary Bladder; Urinary Bladder, Neurogenic; Urodynamics