Solifenacin Treatment After Intradetrusor Injections With Botulinum Toxin in Patients With Neurogenic Detrusor Overactivity.

BACKGROUND: Neurogenic detrusor overactivity (NDO) is treated with antimuscarinics as first-line treatment. For patients with contraindications or unresponsive, intradetrusor injections with botulinum toxin (BoNT) are a safe and effective but expensive option. STUDY QUESTION: Our study evaluated whether adding solifenacin to the intradetrusor injection of BoNT A could boost the effect of BoNT in patients with NDO due to multiple sclerosis or spinal cord injury refractory to antimuscarinics alone and/or lead to less frequent injections. STUDY DESIGN: We performed a prospective study on 49 patients assigned alternatively to group A, undergoing BoNT injections, and group B, adding solifenacin. MEASURES AND OUTCOMES: We gathered data from urodynamic testing and questionnaire assessments before and 3 months after injections and reinjections. We analyzed 39 patients who achieved total continence and a minimum 24-month follow-up period. RESULTS: After treatment, both groups had statistically significant improvement of overactive bladder questionnaire (OABq) score, post void residue (PVR), and peak detrusor pressure (Pdet). Reinjection was needed after a mean 8.2 months for group A and 11.7 months for group B. We analyzed the improvement rate of parameters compared between the 2 groups-group B had greater OABq score improvement (A = 17.25 ± 5.07, B = 20.44 ± 4.51, P = 0.0485), as well as for maximum bladder capacity (A = 11.05 ± 7.04 mL, B = 19.39 ± 6.43 mL, P = 0.0005); differences in Pdet change (A = 51.72 ± 16.57 cmH 2 O, B = 50.80 ± 16.33 cmH 2 O, P = 0.7635) and PVR change (A = 17.67 ± 12.63 mL, B = 12.30 ± 8.32 mL, P = 0.126) were not statistically significant. CONCLUSIONS: Our study shows that adding solifenacin improves patient satisfaction, increases the interval between reinjections, thus lowering costs, and improves maximum bladder capacity. Pdet was kept in safe ranges, but no statistically significant conclusions could be drawn regarding Pdet and PVR decrease related to adding solifenacin. Although our study is limited by the small series of patients and lack of randomization and placebo control group, the BoNT-solifenacin combination could be considered in NDO in terms of cost-effectiveness. Further studies would be beneficial.

The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.

BACKGROUND: Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy. OBJECTIVE: The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO. METHODS: The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual. RESULTS: A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and ß3-adrenoceptor-agonists possessed good effectiveness and safety. CONCLUSION: OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and ß3-adrenoceptor-agonists have good effectiveness and safety.

IncobotulinumtoxinA versus onabotulinumtoxinA intradetrusor injections in patients with neurogenic detrusor overactivity incontinence: a double-blind, randomized, non-inferiority trial.

BACKGROUND: A randomized, double-blind, non-inferiority clinical study was performed on the efficacy and tolerability of IncobotulinumtoxinA (Incobot/A) vs. OnabotulinumtoxinA (OnabotA) intradetrusor injections in patients with refractory neurogenic detrusor overactivity incontinence performing intermittent catheterization. METHODS: Sixty-four patients with spinal cord injury (SCI) or multiple sclerosis were randomized to receive 30 intradetrusor injections of Incobot/A or OnabotA 200 U; 28 patients in incobotulinumtoxinA group and 29 in onabotulinumtoxinA group completed the study. Primary outcome measure was the non-inferior variation from baseline in daily urinary incontinence episodes (week 12), with a non-inferiority margin of one episode/day. Secondary outcomes measures were changes in Incontinence- Quality of Life questionnaire, Visual Analog Scale Score (bother of symptoms on Quality of Life), urodynamic parameters, occurrence of adverse effects and related costs (week 12). RESULTS: At week 12, mean value of difference in urinary incontinence episodes/day between the two groups was -0.2 (95% two-sided CI: -1; 0.7); the difference in incontinence episodes/day between the two groups was -0.4 with a higher limit of one-sided 95% CI of 0.2 episodes/day which was much lower than the non-inferiority margin of one episode/day. Total score and subscores of Incontinence- Quality of Life questionnaire, Visual Analog Scale scores and urodynamics did not show differences between the two groups. Adverse effects were similar for both treatments, with urinary tract infection being the most frequent, localised effect. Minor costs were observed following Incobot/A. CONCLUSIONS: In patients with refractory neurogenic incontinence due to SCI or multiple sclerosis, incobotulinumtoxinA was not inferior to onabotulinumtoxinA in improving clinical and urodynamic findings in the short-term follow-up, with comparable adverse effects but minor costs.

The M2-muscarinic receptor inhibits the development of streptozotocin-induced neuropathy in mouse urinary bladder.

We investigate the role of M(2)-muscarinic receptors in maintaining neurogenic bladder contraction during hyperglycemia. Mice were injected with a single dose of streptozotocin (125 mg/kg), and neurogenic contraction of urinary bladder from wild type and M(2)-muscarinic receptor knockout (M(2) KO) mice was measured at 8 to 24 weeks after treatment. In wild-type bladder lacking urothelium, the summation of the cholinergic (64%) and purinergic (56%) components of the electrical-field-stimulated response exceeded 100%, indicating a reserve capacity. Although the cholinergic component was slightly less in the M(2) KO mouse, the total electrical-field-stimulated contraction was the same as wild type. The cholinergic and purinergic components of contraction in wild-type bladder were minimally affected by streptozotocin treatment. In M(2) KO bladder, streptozotocin treatment reduced both the cholinergic (after 8-9 and 20-24 weeks) and purinergic (after 20-24 weeks only) components. The loss of function was approximately 50 to 70%. Similar results were observed in bladder with intact urothelium. M(2) KO bladder was more sensitive to the relaxant effect of isoproterenol compared with wild type, and this difference significantly increased at the early and late time points after streptozotocin treatment. In the presence of urothelium, however, this difference in isoproterenol sensitivity was smaller with streptozotocin treatment, but this trend reversed over time. Our results show that M(2) receptors oppose urinary bladder distension in wild-type bladder and inhibit streptozotocin-induced neuropathy.

Paraplegia following image-guided transforaminal lumbar spine epidural steroid injection: two case reports.

OBJECTIVE: To present two case reports of a rare but devastating injury after image-guided, lumbar transforaminal injection of steroids, and to explore features in common with previously reported cases. BACKGROUND: Image (fluoroscopic and computed tomography [CT])-guided, lumbar transforaminal injections of corticosteroids have been adopted as a treatment for radicular pain. Complications associated with these procedures are rare, but can be severe. CASE REPORTS: An 83-year-old woman underwent a fluoroscopically guided, left L3-L4, transforaminal injection of betamethasone (Celestone Soluspan). A 79-year-old man underwent a CT-guided, right L3-L4, transforaminal injection of methylprednisolone (DepoMedrol). Both patients developed bilateral lower extremity paralysis, with neurogenic bowel and bladder, immediately after the procedures. Magnetic resonance imaging scans were consistent with spinal cord infarction. There was no evidence of intraspinal mass or hematoma. CONCLUSION: These cases consolidate a pattern emerging in the literature. Distal cord and conus injury can occur following transforaminal injections at lumbar levels, whether injection is on the left or right. This conforms with the probability of radicular-medullary arteries forming an arteria radicularis magna at lumbar levels. All cases used particulate corticosteroids, which promotes embolization in a radicular artery as the likely mechanism of injury. The risk of this complication can be reduced, and potentially eliminated, by the utilization of particulate free steroids, testing for intra-arterial injection with digital subtraction angiography, and a preliminary injection of local anesthetic.

Anterior lumbosacral polyradiculopathy after intrathecal administration of methotrexate.

Transient paraparesis has been reported with intrathecal chemotherapy agents and the most common cause is an incomplete inflammatory myelopathy. We report a case of a 30-year-old man diagnosed with acute lymphoblastic leukaemia who developed subacute anterior lumbosacral polyradiculopathy following intrathecal methotrexate, an unusual complication of intrathecal chemotherapy in adults. Spinal magnetic resonance discarded myelopathy. Cerebrospinal fluid exam showed elevation of protein, mononuclear pleocytosis and immunoglobulin synthesis. Electrodiagnostic study showed alterations of sensory and motor conductions only in lower limbs, consistent with multilevel radiculopathy. Differential diagnosis included toxic and neoplastic polyradiculopathy, and axonal variant of acute inflammatory demyelinating polyradiculoneuropathy. The authors review possible pathogenic mechanisms and propose several therapeutic and preventive options.

'Street ketamine'-associated bladder dysfunction: a report of ten cases.

Ten young ketamine abusers presented with lower urinary tract symptoms to two regional hospitals in Hong Kong. Investigations demonstrated contracted bladders and other urinary tract abnormalities. These types of findings have never been reported before in ketamine abusers. The possible aetiology is also discussed.

Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats.

1. We have developed and characterized a model of immediate hypersensitivity/inflammation of the urinary bladder in vivo induced by local application of ovalbumin (OA) in OA- sensitive female rats. Two parameters of the inflammatory response were assessed following OA challenge: plasma protein extravasation (PPE) and changes in smooth muscle reactivity. The former was estimated by measurement of Evans blue extravasation at 0.5, 2, 4, 8 and 24 h time point following in vivo challenge. Changes in reactivity were determined by measurement of isotonic tension responses of urinary bladder strips following OA challenge in vitro. 2. Acute in vivo intravesical OA challenge (10 mg in 0.3 ml saline) in actively sensitized female Wistar rats caused a time-dependent PPE in the urinary bladder which was biphasic with peak responses at 2-4 and 24 h. 3. The PPE response to acute OA challenge, above base-line, at 2 h was abolished by systemic capsaicin pretreatment (50 mg kg(-1), s.c., 4 days before use) (P < 0.05) whilst the response at 24 h was unaffected. The 2 h time point was then used for further studies. 4. Degranulation of mast cells, achieved by pretreatment with compound 48/80 (5 mg kg(-1), s.c. for 3 consecutive days), completely abolished the PPE response to OA challenge at the 2 h time point. 5. The tachykinin NK1 receptor antagonist, SR 140333 (0.1 micromol kg(-1), i.v.), abolished the 2 h PPE response whilst the tachykinin NK2 receptor antagonist MEN 11420 (0.1 micromol kg(-1), i.v.) appeared to reduce the response by approximately 50% but this did not reach significance. The bradykinin B2 receptor antagonist, Hoe 140 (0.1 micromol kg(-1), i.v.), similarly to SR 140333, blocked the 2 h PPE response to OA, whereas the selective B1 receptor antagonist B 9858 (0.1 micromol kg(-1), i.v.) had no significant effect. Inhibition of cyclo-oxygenase (COX) achieved by pretreatment with the COX inhibitor dexketoprofen (5.3 micromol kg(-1), i.v.) also blocked the PPE response, whilst the leukotriene receptor antagonist ONO 1078 (1 micromol kg(-1), i.v.) significantly reduced PPE by about 80%. 6. In the rat isolated urinary bladder OA (1 mg ml(-1)) challenge produced a biphasic response with a rapidly achieved maximal contraction followed by a sustained contraction for approximately 25 min. In vitro capsaicin pretreatment (10 microM for 15 min) significantly attenuated the duration of the sustained contraction whilst having no effect on the maximum contractile response achieved. In vivo pretreatment of animals with compound 48/80 significantly attenuated (42%) the maximum contractile response. Combination of both treatments almost completely abolished the response. In vitro treatment with Hoe 140 (1 microM) had no significant effect on the response to OA and neither did ONO 1078 (1 microM). 7. These results show that both the early inflammatory response and alterations in smooth muscle reactivity to OA challenge in actively sensitized animals are dependent on mast cell degranulation and the activation of sensory C-fibres. Furthermore this model of allergic cystitis may be useful for investigating both the processes involved and potential novel therapies in the treatment of interstitial cystitis.

Prevention of toxic environmental illness in the twenty-first century.

Previous introductions of new technologies have frequently resulted in unanticipated occupational and environmental illness. Prevention of such illness in the twenty-first century requires stringent application of two fundamental principles of public health: evaluation of new technologies before their introduction, and surveillance of exposed persons after the introduction of new technologies. Failure to establish these basic preventive mechanisms in advance will inevitably result in the development of new toxic diseases in the twenty-first century.

Tricyclic exacerbation of undiagnosed diabetic uropathy.

A case of probable exacerbation of an undiagnosed diabetic uropathy by a tricyclic antidepressant in a 67-year-old man with hypothyroidism, diabetes mellitus, and recurrent major depressive disorder is reported. The presumed mode of interaction is discussed and pertinent literature reviewed. It is emphasized that the clinician must be alert to the possibility of psychotropic drugs producing physiologic changes that can interact with or aggravate preexisting disorders.

Inadequacies and hazards of chymopapain injections as treatment for intervertebral disc disease.

Chymopapain chemonucleolysis was performed on 100 patients with primary lumbar intervertebral disc disease. The results were compared with those of 174 patients who underwent laminotomy, foraminotomy, and discectomy. Primary lumbar intervertebral disc disease was arbitrarily divided into degenerative, complex, previous surgical, and simple disc syndromes. No difference was seen between chemonucleolysis and surgery in the first three divisions; between 55 percent and 60 per cent of patients responded successfully to treatment. In the simple disc division 89 per cent of the surgical and 60 per cent of the chemonucleolysis patients had successful results.

Reversible urinary retention secondary to excessive morphine delivered by an intrathecal morphine pump.

Reversible complication of intrathecal morphine delivered by an implanted pump is described in one patient. The patient was evaluated initially using a contrast CT of the thoracic spine as well as urodynamics studies. After decreasing the intrathecally administered morphine from 2 mg/24 hr to .5 mg/24 hr, the patient's neurogenic bladder reversed within 4 days. Implanted pumps to deliver intrathecal narcotic medications are being used currently to treat intractable pain. This is a case report of reversible urinary retention secondary to the intrathecal narcotic.

[The medication-induced dysfunction of the urinary bladder]. / Die medikamenteninduzierte Dysfunktion der Harnblase.

Bladder dysfunction can result from pathological changes in the bladder itself, of its central neurological regulation, (BPS), or of non-urological diseases such as diabetes or heart failure. Medication-induced bladder dysfunction can mostly be treated by simple changes in the pharmacological therapy. Bladder dysfunction can be induced pharmacologically by activating or inhibitory influences on adrenergic, sympathetic, beta-receptor-induced relaxation of the detrusor, alpha-receptor-induced contraction of the bladder neck, or cholinergic, parasympathetic, muscarinic receptor-induced contraction of the detrusor. Diuretics can increase urine production, thus possibly leading to incontinence. If incontinence occurs in patients, treatment should be stopped if possible and additional pharmacological therapy should not be started before medication-induced bladder dysfunction is excluded.

Neurogenic bladder and chronic urinary retention associated with MDMA abuse.

INTRODUCTION: The use of 3,4-methylenedioxymethamphetamine (MDMA, known as "ecstasy"), a synthetic amphetamine and "club drug," has been associated with acute, transient urinary retention. We report a case of neurogenic bladder and chronic urinary retention associated with MDMA abuse. CASE REPORT: A 21-year-old male presented to the emergency department (ED) because he had abdominal pain and difficulty urinating. He had experienced difficulty in initiating urination over the past 1.5 months, with periods of 24 to 36 hours between voids and large volumes of urine. The patient had a chronic pattern of MDMA use, taking 4 tablets/day for 3 months. Two weeks before coming to the ED, he had been admitted to an inpatient drug rehabilitation center. During the time since that admission, the patient had visited EDs repeatedly for insertion and removal of Foley catheters to relieve the urinary retention until he could be admitted to a urologic service. Cystometrogram was abnormal, finding no sensation of bladder fullness after instillation of 350 mL of saline and inability to generate a voluntary voiding pressure. Cystoscopy revealed no outlet obstruction. The findings were consistent with neurogenic bladder. The patient was given prescriptions for bethanecol and phenazopyridine, and told to continue a 10-day course of sulfamethoxazole/trimethoprim for urinary tract infection. He was discharged with a Foley catheter in place. Symptoms of urinary retention persisted at 1-year follow-up, despite self-catheterization and complete cessation of MDMA use. CONCLUSION: Chronic MDMA use may lead to neurogenic bladder and chronic urinary retention.

Vincristine-induced peripheral neuropathy and urinary bladder paralysis in a child with rhabdomyosarcoma.

Vincristine commonly induces peripheral neuropathy but rarely causes voiding dysfunction. In this report, we describe a case of neurogenic bladder and peripheral neuropathy caused by the neurotoxic effect of vincristine and documented by urodynamic testing and electromyography. Neurologic evaluation aided in monitoring and understanding this problem.

Acute vs chronic effects of l-dopa on bladder function in patients with mild Parkinson disease.

OBJECTIVE: To compare acute and chronic effects of l-dopa on bladder function in levodopa-naive Parkinson disease (PD) patients who had urinary urgency. METHODS: We evaluated 26 l-dopa-naive PD patients at a university-based PD center with a first urodynamic session with a double examination: in the off treatment condition and 1 hour after acute challenge with carbidopa/l-dopa 50/200 mg; then, a chronic l-dopa monotherapy was administered (mean dose 300 +/- 150 mg). Two months later, patients underwent a second urodynamic session with a single evaluation 1 hour after the acute carbidopa/l-dopa challenge. RESULTS: The first acute l-dopa challenge significantly worsened bladder overactivity (neurogenic overactive detrusor contractions threshold [NDOC-t; 32% of worsening] and bladder capacity [BC; 22% of worsening]); on the contrary, l-dopa challenge during chronic administration ameliorated the first sensation of bladder filling (FS; 120% of improvement), NDOCT-t (93% improvement), and BC (33% of improvement) vs the values obtained with acute administration. An 86% significant improvement of FS in comparison with the basal value was observed. CONCLUSIONS: The acute and chronic l-dopa effects may be due to the different synaptic concentrations or to the activation of postsynaptic mechanisms obtained by chronic administration.