Background Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox® (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administrati...

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Use of botulinum toxin in individuals with neurogenic detrusor overactivity: State of the art review

Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment.

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Autonomic Dysregulation in Multiple Sclerosis

Botulinum toxin A (BoNTA) is increasingly used for therapy of neurogenic detrusor overactivity (NDO) refractory to antimuscarinics or where patients are experiencing antimuscarinic-related side effects. The objective was to compare and critically discuss the reported efficacy and safety of BoNTA in adults with neurogenic bladder dysfunction. Studies published between January 1985 and July 2012 were identified in the MEDLINE (PubMed) and SCOPUS databases. A search for studies with onabotulinumtoxinA—the only formulation of BoNTA approved by the US FDA in adults with NDO—was performed. Exclusion criteria were urethral sphincter injection, no separate analysis between onabotulinumtoxinA and other formulations of BoNTA, mean follow-up ≤4 weeks and studies with ten or fewer patients. Clinical and urodynamic parameters for efficacy, adverse events (AEs) and tolerability were reviewed to offer recommendations for practice and future research. A total of 28 included studies revealed superior effects of onabotulinumtoxinA compared with placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters and health-related quality of life. The most frequently reported AEs were de novo intermittent catheterization, urinary retention and asymptomatic urinary infection. Limitations of this review are the inclusion of studies with the level-3 evidence (22/28 studies), the heterogenicity of outcome parameters and time points chosen for follow-up reported in the reviewed studies. OnabotulinumtoxinA therapy is effective, safe and well tolerated in adults with neurogenic bladder dysfunction. Further high-quality prospective trial data are required to determine the optimal dose, injection technique, long-term safety, favourable timing, indications for re-injections, and the impact of concomitant antimuscarinics on onabotulinumtoxinA therapy.

Efficacy and Safety of Botulinum Toxin A Intradetrusor Injections in Adults with Neurogenic Detrusor Overactivity/Neurogenic Overactive Bladder: A Systematic Review

This is a systematic review on the treatment of lower urinary tract symptoms (LUTS) in patients with multiple sclerosis (MS). The heterogeneity of the outcome criteria did not allow a meta-analysis of the published evidence. In the last few decades, the therapeutic options for neurogenic bladder dysfunction have broadened. Despite this, no consensus has been reached as to the management of LUTD and LUTS in patients with MS, and the subject remains controversial. Bladder dysfunction is common in MS, affecting 80 %–100 % of patients during the course of the disease. Several studies have shown that urinary incontinence has a severe effect on patients’ quality of life, with 70 % of patients classifying the impact bladder symptoms had on their life as “high” or “moderate.” Moreover, the progressive feature of MS makes its treatment complex, since any achieved therapeutic result may be short-lived, with the possibility that symptoms will recur or develop de novo.

The treatment of lower urinary tract symptoms in patients with multiple sclerosis: a systematic review.

Multiple sclerosis (MS) can be a debilitating neurological condition that attributes significant morbidity to bladder dysfunction. Although many effective treatment options exist, symptomatic patients are often underdiagnosed and undertreated. The purpose of this article is to give an overview of the current literature including new screening tools to identify symptomatic patients and updates on treatment options including medications, botulinum toxin, and neuromodulation.

Management of Neurogenic Lower Urinary Tract Dysfunction in Multiple Sclerosis Patients

Purpose: Neurogenic detrusor overactivity (NDO) is common in patients who suffer from multiple sclerosis (MS). When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A) injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. Materials and Methods: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor), improvement, or total failure (urge incontinence and overactive detrusor). Results: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001), maximum cystometric capacity (p = 0.0035), maximum detrusor pressure (p = 0.0000001). 46% of the patients were in the “full success” group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015). Conclusions: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

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M. Weil

Papers

Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.