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The prevalence of nocturia in patients with multiple sclerosis (MS) is high, ranging from 20.9% to 48.8% in this population. Its underlying pathophysiology is complex and different from the non-neurogenic population. In the MS population, the pathophysiology may involve neurogenic lower urinary tract dysfunction (NLUTD) such as detrusor overactivity (NDO), detrusor-sphincter dyssynergia, or detrusor underactivity resulting in reduced bladder capacity. Nocturnal polyuria is also a significant contributor to the pathogenesis of nocturia in MS patients and may be the result of specific mechanisms such as nocturnal hypertension through autonomic cardiovascular dysfunction or lack of diurnal variation of antidiuretic hormone production (ADH) due to demyelinating lesions of the spinal cord. Nocturia might be particularly burdensome in MS patients by contributing to fatigue, a common and highly debilitating symptom in this population. There is likely a complex and multidirectional relationship between nocturia, other sleep disorders, and fatigue in the MS population that has yet to be explored. The assessment of nocturia in MS should rely upon a thorough history and physical examination. Urinalysis should be done to rule out urinary tract infection, a frequency-volume chart might help elucidating the underlying mechanisms, and post-void residual volume may be of interest to screen for urinary retention that could be asymptomatic in MS patients. Other tests such as urodynamics or polysomnography are indicated in selected patients. The treatment should be tailored to the underlying cause. The first steps involve behavioral interventions and treatment of cofactors. When possible, the predominant mechanism should be addressed first. In case of predominant NDO, antimuscarinics and beta-3 agonists should be offered as a first-line treatment and intradetrusor injections of botulinum toxin as a second-line treatment. In cases of incomplete bladder emptying, clean-intermittent self-catheterization is often used as part of multiple other interventions. In cases of nocturnal polyuria, desmopressin may be offered, inclusive of use of newer formulations (desmopressin acetate nasal spray, desmopressin orally disintegrated tablet) in countries where they are approved., (© 2019 MedReviews®, LLC.)

Nocturia is a complex condition that not only significantly affects quality of life, but may be an indicator of systemic disease. Initial assessment includes a detailed history and physical examination and completion of a frequency volume chart to help identify underlying causes, such as sleep disorders, bladder storage disorders, and polyuria. Treatment with alpha-blockers or antimuscarinic medications may help if the underlying cause is determined to be benign prostatic hyperplasia or overactive bladder, respectively. Treatment options for nocturnal polyuria have been limited to behavioral therapy and off-label use of timed diuretics and desmopressin. Desmopressin acetate nasal spray (Noctiva™, Avadel Pharmaceuticals, Chesterfield, MO) was approved by the US Food and Drug Administration in 2017 for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least twice nightly and has shown efficacy in reducing nocturnal voids by ≥50% in up to 49% of patients in clinical trials.

In clinical trials, transdermal oxybutynin (OXY-TDS) has shown comparable efficacy and improved tolerability when compared with conventional pharmacotherapy. Systemic anticholinergic adverse effects are comparable to those with placebo, most likely owing to avoidance of first-pass hepatic metabolism and conversion of oxybutynin to N-desethyloxybutynin. OXY-TDS has predictable pharmacokinetic absorption and elimination parameters, as shown in both in vitro and in vivo studies. Consistent plasma concentrations of oxybutynin avoid labile peak and trough concentrations seen with immediate-release formulations, paralleling extended-release drug delivery. This novel drug delivery system has unique dermatologic skin application site reactions, including erythema and pruritus. Skin reactions are usually mild and can be minimized by varying the site of patch application. Most eczematous dermatologic reactions can be appropriately treated with a moderately potent topical corticosteroid cream. A small percentage of patients will discontinue therapy as a result of bothersome application site skin reactions.

Numerous gender-specific etiologies are responsible for bladder outlet obstruction (BOO). BOO may be induced by specific functional and anatomic causes. The resulting obstruction frequently produces lower urinary tract symptoms (LUTS). Categorizing and understanding these entities is crucial when proceeding with a LUTS evaluation as specific diagnostic modalities may then be used to fully delineate the degree of BOO and any secondary issues. Although urodynamic evaluation and pressure flow evaluation is the gold standard diagnostic tool, other modalities may also be used, including post void residual analysis, urinary flow rates, cystoscopy, and selected radiologic ones. Patient self-appraisal of symptoms using various inventories such as the American Urologic Association Symptom Index or the International Prostate Symptom Score is relevant to the initial assessment and subsequent longitudinal follow up. Analysis of secondary symptoms of obstruction in women is often performed using a subjective symptom appraisal and is determined urodynamically, assessing the pressure-flow relation during voiding. The complete assessment of LUTS arising from BOO often includes several of these modalities to fully define the obstructive impact on the individual's urinary function and quality of life.

Advances in materials technology, coupled with a heightened understanding of wound healing and tissue-materials interactions in the lower urinary tract, have led to the development of a variety of new urethral bulking agents that are expected to be available in the near future. Experience with such bulking agents continues to grow and study results are disseminated as more clinical trials are initiated and completed. The intention of this report is to review the characteristics and initial clinical results for one of these new agents: Tegresstrade mark Urethral Implant (C. R. Bard, Inc., Murray Hill, NJ). This material, with unique phase-change properties upon exposure to body temperature fluids, offers ease of injection and requires less volume for clinical effect than bovine collagen. Additionally, Tegress Urethral Implant performance in clinical trials has suggested improved durability and correspondingly higher continence and improvement rates versus bovine collagen. As these materials evolve, an understanding of preferential implant techniques is being gained also. Delivery method and implant site may prove to substantially alter the biologic activity of these compounds. As outlined in this review, experience with Tegress Implant resulted in changes in delivery technique that translated into improved materials and tissue interaction.

Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.

The understanding and management of overactive bladder (OAB) continue to evolve. However, argument persists as to the exact incidence of the disease and the underlying pathophysiology of the symptom complex. Individual differences in symptomatic impact and, more importantly, personal coping partially account for the disparity noted among demographic estimates currently extant. Likewise, the underlying pathophysiology that leads to overt OAB syndrome is, as yet, incompletely characterized. Muscarinic receptor behavior provides partial explanation, but other complex underlying receptor and neurotransmitter interactions probably are also a component of the presentation. Current state-of-the-art therapy relies on an exclusionary diagnosis prior to the inception of therapy. Ideally, optimal therapy involves behavioral and pharmacologic interventions combined to maximize therapeutic results. Antimuscarinic therapy provides only a degree of relief from the bothersome symptoms of OAB. As yet, few options exist for patients who have previously failed oral antimuscarinic intervention. Herein, the evolving OAB landscape will be considered as it currently stands in 2003. The current lack of optimal symptom control will most assuredly lead to the development of new pathways for OAB treatment.