Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases.

Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration).

Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality.

Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment. Investigational drug targets and compounds are also reviewed. We conclude that, despite a range of available medical treatment options, a considerable medical need continues to exist. This is largely because the existing treatments are symptomatic and have limited efficacy and/or tolerability, which leads to poor long-term adherence. SIGNIFICANCE STATEMENT: Urinary incontinence and related disorders are prevalent in the general population. While many treatments have been approved, few patients stay on long-term treatment despite none of them being curative. This paper provides a comprehensive discussion of existing and emerging treatment options for various types of incontinence and related disorders.

Introduction: Desmopressin was widely used to treat nocturnal polyuria in adults under the age of 65 due to the well-established risk of hyponatremia. Since the prevalence of nocturia increases with age, and with an aging population, those most affected were excluded from treatment. Recently, a new lower dose sublingual tablet formulation that optimizes the balance between efficacy and tolerability has been licensed for symptomatic treatment of nocturia due to idiopathic nocturnal polyuria in adults of any age, with the caveat of regular serum monitoring for those over 65. This newer formulation aims to achieve the same clinical outcomes as previous formulations while reducing the risk of hyponatremia.Areas covered: This review will look at the pharmacology of the newly formulated desmopressin and examine the results of the clinical trials that would support its treatment of adult nocturia with idiopathic nocturnal polyuria.Expert opinion: When reporting on the clinical efficacy of desmopressin on nocturia, it is important for clinical trials to publish their complete data on nocturnal and 24-hour urine voided volumes. Further research examining the physiological reasoning behind this gender-specific dosing for desmopressin and the optimal recommended treatment duration of desmopressin for those over 65 is needed.

Nocturia is among the most common and bothersome lower urinary tract symptoms (LUTS), but there is no clear consensus on how to identify and manage this symptom in the neurological population.

To systematically review the literature about nocturia in neurological patients.

Studies were identified by electronic search of Cochrane and Medline databases. The studies were included if their participants had acquired neurological pathology among multiple sclerosis (MS), Parkinson's disease (PD), stroke, spinal cord injury (SCI), and reported data on the epidemiology, aetiology, diagnosis, or treatment of nocturia. An independent extraction of the articles was performed by two authors using predetermined datasets, including quality-of-study indicators.

A total of 132 studies were included; 46 evaluated the epidemiology of nocturia, 28 the possible aetiologies, 10 the diagnostic tools, and 60 the treatments. Nocturia prevalence ranged from 15% to 96% depending on the pathology and definition used. It was one of the most frequently reported LUTS in PD and stroke patients. Several validated questionnaires were found to screen for nocturia in this population. Causalities were numerous: LUT, renal, sleep, cardiovascular dysfunctions, etc. Treatments targeted these mechanisms, with an overall risk of bias assessed as high or serious. The highest level of evidence was seen in MS patients: pelvic floor muscle training, cannabinoids, and desmopressin were effective, but not melatonin. In stroke patients, transcutaneous sacral and transcutaneous tibial nerve stimulation (TTNS) improved nocturia; in PD patients, TTNS, solifenacin, and rotigotine did not.

Nocturia is highly prevalent in patients with neurological disorders. Causalities and treatments are not different from the general population, but are poorly studied in neurological patients.

In this report, we looked at the published studies about nocturia-the fact of waking to void during the hours of sleep-in patients with neurological diseases. We found that nocturia is very frequent in this population, that the causes are the same as in the general population but may be combined, and that treatments are also the same but have an overall weak level of evidence. We conclude that more research is needed on this topic.

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.

Nocturia, defined as waking at night to pass urine, is a common condition which increases with age. Whilst nocturia is known to have an important effect on quality of life, more recent evidence has linked the symptom with significant morbidity and mortality due to the effects of sleep deprivation on glucose metabolism and the immune system. The causes of nocturia are multifactorial and may be related to urine overproduction, storage disorders and primary sleep disorders. The commonest underlying pathology, however, is nocturnal polyuria, which may be associated with a number of medical conditions. This review explores the underlying causes of nocturia and nocturnal polyuria and, by doing so, describes a multidisciplinary approach to managing patients effectively.

To address targeting and bioavailability issues of peptidic drugs like desmopressin, the encapsulation into nanoparticles (NP) has become standard in pharmaceutics. This study investigated the encapsulation of desmopressin into PLGA NP by the use of pharmaceutically common stabilizers as a precursor to future, optional targeting and bioavailability experiments. Polymer dry weights were measured by freeze drying and thermo gravimetric analysis (TGA). Particle sizes (ranging between 105 and 130nm, PDI<0.1) and zeta potentials (-35 to -45mV) were analyzed with Dynamic Light Scattering (DLS) and Laser-Doppler-Anemometry (LDA) respectively. Highest loading efficiencies, quantified by RP-HPLC, were achieved with Pluronic F-68 as stabilizer of the inner aqueous phase (1.16±0.07μg desmopressin/mg PLGA) and were significantly higher than coating approaches and approaches without stabilizer (0.74±0.01μg/mg). Optimized nanoformulations are thus in competition with the concentration of commercial non-nanoparticulate desmopressin products. Stability of desmopressin after the process was evaluated by HPLC peak purity analysis (diode array detector) and by mass spectrometry. Desmopressin was shown to remain intact during the whole process; however, despite these very good results the encapsulation efficiency turned out to be a bottle neck and makes the system a challenge for potential applications.

Desmopressin is a synthetic analogue of arginine vasopressin, commercially available since 1974. Desmopressin is proven effective for the treatment primary nocturnal enuresis and polyuria. It has been considered by several investigators for the treatment of nocturia with positive results and is now an established treatment for this indication. In this review, we assessed the available clinical data on desmopressin in adult urological disease.

The range of symptoms which occur in multiple sclerosis (MS) can have disabling functional consequences for patients and lead to significant reductions in their quality of life. MS symptoms can also interact with each other, making their management challenging. Clinical trials aimed at identifying symptomatic therapies have generally been poorly designed and have tended to be underpowered. Therefore, the evidence base for the management of MS symptoms with pharmacologic therapies is not strong and tends to rely upon open-label studies, case reports, and clinical trials with small numbers of patients and poorly validated clinical outcome measures. Recently, there has been a growing interest in the management of MS symptoms with pharmacologic treatments, and better-designed, randomized, double-blind, controlled trials have been reported. This chapter will describe the evidence base predominantly behind the various pharmacologic approaches to the management of MS symptoms, which in most, if not all, cases, requires multidisciplinary input. Drugs routinely recommended for individual symptoms and new therapies, which are currently in the development pipeline, will be reviewed. More interventional therapies related to symptoms that are refractory to pharmacotherapy will also be discussed, where relevant.

Since lower urinary tract dysfunction (LUTD) related to multiple sclerosis (MS) has a different behavior pattern than other types of neurogenic voiding dysfunction, we aimed to prepare a national consensus report for the management of LUTD due to multiple sclerosis in light of available literature.

A search of available databases yielded an evidence base of 125 articles after the application of inclusion/exclusion criteria. When sufficient evidence existed, recommendations A (high), B (moderate), or C (low) were made according to the strength of evidence; recommendation D was provided when insufficient evidence existed.

Available data did not support the use of invasive urodynamics in the initial evaluation of patients with MS and LUTD. Clinical studies on the safety and efficacy of antimuscarinics and alpha-blockers in these patients were scarce and low quality. Desmopressin could be used in MS-related overactive bladder symptoms owing to its short-term effects as an adjunctive treatment. Intravesical botulinum toxin type A treatment in patients with MS and detrusor overactivity was recommended in cases of medical treatment failure or severe side effects due to antimuscarinics. Pelvic floor rehabilitation together with neuromuscular electrical stimulation was also recommended as it increased symptomatic treatment success. This systematic review was not able to find any evidence-based cut off post-void residual value for the recommendation to start clean intermittent catheterization in MS-related LUTD.

Patients with MS and LUTD could be best managed through the use of this consensus report.

Arginine vasopressin (AVP), also known as vasopressin or anti-diuretic hormone, is a neuropeptide produced in the hypothalamus. It is primarily responsible for osmoregulation and thus maintains body fluid homeostasis. It is also a potent vasoconstrictor, may have a role in higher cognitive functions and affects metabolism. All the biological and cellular effects of vasopressin are mediated by the interaction of this hormone with three G-protein-coupled receptors - V(1a), V(1b) and V(2).Urological applications are based on the rationale that V(2) receptors mediate water conservation and increase urine osmolality. Due to their anti-diuretic properties mediated by the V(2) receptors, synthetic vasopressin agonists, such as desmopressin, are now commonly used for the treatment of nocturnal polyuria, central diabetes insipidus and nocturnal enuresis and potentially in urinary incontinence. Desmopressin has been licenced worldwide for haematological indications of haemophilia and von Willebrand disease. Vasopressin receptor antagonists correct hyponatremia by blocking the activation of the V(2) receptor and induce a free water diuresis without an accompanying natriuresis or kaliuresis; an effect termed 'aquaresis'. Interfering with vasopressin signalling by administering vasopressin antagonists may have clinical benefits in acute and chronic heart failure.

The occurrence of urogenital dysfunction as an isolated early symptom in multiple sclerosis (MS) is rare, but the prevalence thereof becomes high with progression of disease. Lower urinary tract dysfunction may add to the cause of death (particularly through urinary infections), but both urinary and sexual dysfunction significantly affect quality of life of patients. Both storage and evacuation of urine may be affected by MS, and ultimatively the functional diagnosis can only be made by urodynamic testing. As upper urinary tract affection is, however, rare (and can be prevented by timely ultrasound imaging), a first stage diagnostics in the MS center by the neurologist and specialized nurse is appropriate. History, urine tests and post void residual urine determination (preferably by ultrasound) should provide necessary data for treatment of infections, and also symptomatic management of frequency, urgency and incontinence by bladder training, anticholinergics, and intermittent self catheterization (as indicated); the referral to urologist may be reserved for patients who fail first line treatment. Treatment in the late stages of MS is as yet little researched, but eventually a suprapubic catheter is the preferred method of bladder emptying. Sexual dysfunction should be actively sought in MS patients (in men erectile and ejaculation dysfunction, in women deficient lubrication and genital hyper- or hyposensitivity are frequent). Clinical examination contributes little to clarification of neurogenic sexual dysfunction, but defines the extent of other deficits due to MS, which may be relevant for sexual counseling (spasticity, sensory loss). Sildenafil has been demonstrated to be effective in treatment of men, but not in women. Other management options exist, and the doctor and nurse in the MS center should be proactive in providing first line counseling and management.

This study looked at whether oral desmopressin, by decreasing kidney urine production, would prolong bladder filling-time thereby increasing the time to reach maximum capacity, thus reducing overactive bladder (OAB) symptoms, and providing an alternative method of treatment to OAB sufferers.

An investigator-initiated, 2-week, multi-national, multi-centre, "proof-of-concept," phase IIb, double-blind, placebo-controlled, prospective, randomized, cross-over study was conducted using 0.2 mg of oral desmopressin in adults suffering with OAB. Patients were included in the trial period if they had >or=4 voids in the first 8-hr of the day after rising, excluding the first morning void. The primary endpoint was evaluation of effectiveness of desmopressin in increasing the time to the first OAB symptom episodes during the first 8-hr following treatment.

Time to first void was 8-min later on the drug than on placebo (P = 0.27). However, the drug led to one less void (3.2 vs. 4.2) in the same period (P < 0.001). There was an increase in the time to first urgency episode with a decrease in the number of urgency episodes in the drug days compared to placebo (P < 0.003). There was a subjective improvement in frequency and urgency and overall quality-of-life as measured by the ICIQ-OAB. Twenty-seven people reported adverse events which were all mild, headache being the commonest and no hyponatremia was recorded.

Antidiuresis, using oral desmopressin tablets, is a novel, feasible and safe (short-term basis) method of treatment for adults with OAB, and could be considered in the armamentarium of drugs available for the treatment of OAB.

Urinary incontinence and lower urinary tract dysfunction, whilst not life threatening conditions, remain an important cause of morbidity in women and are responsible for significant impairment of quality of life. Drug therapy is often used to treat women who complain of urgency and urge incontinence and has an emerging role in the management of stress urinary incontinence. However, bothersome side effects are known to affect compliance and therefore compromise efficacy, making longterm drug therapy unpopular. The principle aim of this thesis is to assess the role of antidiuresis in women complaining of daytime urinary incontinence and also to examine its role as a 'designer therapy' which women can choose to use as, or when, required. In addition both the patients' and clinicians' attitudes towards treatment have been studied to clarify the meaning of 'cure', and to determine treatment acceptability, overall outcome and patient satisfaction. In the first study the patients' concept of cure is explored as well as their expectations regarding treatment and outcome. The second study examines cure from the clinician's perspective in addition to reviewing outcome measures in the clinical and research settings. Finally in the third study the use of desmopressin in women complaining of daytime urinary incontinence is reported.

Overactive bladder (OAB) syndrome is the term used to describe the symptom complex of urinary urgency with or without urge incontinence, usually with frequency and nocturia. Drug treatment continues to have an important role in the management of women with OAB. Other treatment options include conservative management with lifestyle interventions, modification of fluid intake, and physiotherapy including bladder retraining. Surgery remains the last resort in the treatment and is usually reserved for intractable detrusor overactivity, as it is associated with significant morbidity. This article reviews the management of the overactive bladder with specific focus on newer developments in the medical treatment of OAB in women.

Nocturia, the complaint of waking at night to void, is a bothersome condition known to affect Quality of Life. In addition sleep deprivation is also known to affect daytime functioning and productivity. Whilst recently recognised as a discrete clinical entity nocturia is also a symptom of those women complaining of Overactive Bladder (OAB) syndrome. The causes of nocturia are multifactorial although in clinical practice nocturia is generally associated with either increased nocturnal urine production, problems related to bladder storage or sleep pattern abnormalities. When evaluating women complaining of nocturia a urinary diary and clinical examination is integral to making the diagnosis prior to commencing treatment. Having excluded and treated any underlying cause behavioural modification, such as moderation of fluid intake or timing of taking anti-diuretic medication, should be considered first line therapy. Should this conservative approach fail then treatment with antimuscarinic agents or desmopressin, a nona-peptide analogue of anti-diuretic hormone (ADH) is often helpful.

Nocturia is a common source of sleep disturbance in men and can result from many different causes. A patient-generated frequency/volume chart, along with several simple mathematical formulas, is used to classify nocturia according to its principal aetiology. The categories are nocturnal polyuria (NP), reduced voided volumes, 24-h polyuria and a combination of the aforementioned factors. Identification of the precise type of nocturia can help direct treatment in the cause-specific manner. In particular, use of the antidiuretic desmopressin can be of benefit in those with NP and may also be useful as part of a combination treatment approach in nocturia of mixed aetiology.

Overactive bladder (OAB) is a bothersome condition that affects millions of people worldwide. It consists of urgency, incontinence, frequency and nocturia. Treatment, in the form of lifestyle interventions, bladder training and pelvic floor muscle exercises, aim to alleviate symptoms. These treatment modalities have drawbacks, including being time consuming and require stamina on the part of the patient and treating physician. Drugs may be used if conservative measures fail or in combination with them. Antimuscarinics are the mainstay of OAB medication but may cause dry mouth, blurred vision or constipation. It is, therefore, crucial that new treatment modalities are sought to help with this potentially debilitating condition. Antidiuresis, using desmopressin, forms a potential candidate for a novel treatment. As the bladder fills with urine, symptoms of OAB are experienced by patients. It would be reasonable to hypothesise that if the rate of bladder filling is reduced then so would the symptoms of OAB. Desmopressin reduces the production of urine by the kidneys, therefore reducing the amount of urine in the bladder and, therefore, the symptoms of OAB. Desmopressin has been used previously in small single centre trials in neurogenic OAB patients with some success but recently two multi-centre, multinational randomised placebo controlled trials using this concept have been completed in idiopathic OAB sufferers and reported in the literature. The results were quite promising although there were minor side effects. These trials suggest that this potential novel treatment modality for OAB sufferers might avoid the necessity for invasive treatments, such as botulinum toxin, neuromodulation or surgery, in some instances. These trials also open the way to combination therapy with current treatment modalities of OAB.

Abnormalities of micturition occur in many different diseases, have a variety of causes and take several forms. This review will focus exclusively on those abnormalities in which antidiuretic therapy may be of benefit. These conditions are primarily characterized by an increase in the total amount of urine produced (polyuria) or a circadian shift in the control of urine production and/or voiding (nocturnal enuresis, nocturia).

Bladder dysfunction is a common problem for patients with multiple sclerosis. The severity of symptoms often correlate with the degree of spinal cord involvement and, hence, the patient's general level of disability. The emphasis of management is now mainly medical and is increasingly offered by nonurologists. Treatments can be highly effective, relieving patients of what are otherwise very troublesome symptoms that would compound their neurological disability. This article gives an overview of the neural control of the bladder, followed by an explanation of the pathophysiology of detrusor overactivity secondary to neurological disease. A review of methods available for treating bladder dysfunction in multiple sclerosis then follows. The treatment options for this disorder are largely medical and include established first-line measures such as anticholinergics, clean intermittent self-catheterization and the use of desmopressin, as well as potential second-line agents, such as cannabinoids, intravesical vanilloids and intradetrusor botulinum neurotoxin type A. The diminishing role of surgical intervention is also discussed.

Desmopressin, a synthetic antidiuretic hormone analogue, is the only drug currently approved for the treatment of nocturia associated with nocturnal polyuria or multiple sclerosis (MS). Compared with vasopressin, desmopressin has a longer lasting and more potent antidiuretic effect and is devoid of vasopressor and uterotonic effects. In two large, randomised, double-blind phase III trials in adults with nocturia associated with nocturnal polyuria, 3 weeks of oral desmopressin therapy was significantly more effective than placebo in reducing the mean number of nocturnal voids and in normalising the rate of nocturnal urine production. Beneficial effects of desmopressin on nocturia were maintained and increased in patients completing 10 or 12 months of further treatment in a nonblind extension of short-term trials. In randomised, double-blind trials in MS patients with nocturia, nasal desmopressin reduced the mean number of nocturnal voiding episodes by 31-54%. In both patient populations, desmopressin increased the initial sleep period or mean maximum period of uninterrupted sleep by approximately 2 hours, an outcome significantly greater than that achieved with placebo. In trials of < or =6 weeks duration in adults with nocturia, desmopressin was generally well tolerated. Most desmopressin-related adverse events were transient and mild or moderate in severity. Clinically significant hyponatraemia was reported in approximately 5% and required withdrawal from studies in < or =3% of patients.

To investigate the efficacy of desmopressin nasal spray on daytime urinary incontinence in women.

A multicentre, multinational, randomized, double-blind, placebo-controlled, cross-over exploratory study of women (aged 18-80 years) complaining of severe daytime urinary incontinence was conducted in three centres (King's College Hospital; Boras County Hospital and Skejby Hospital). Seventy-five patients were screened of whom 64 were randomized. In all, 60 women received study medication (safety population) and 57 completed the study. The intention-to-treat population comprised 59 patients and there were 41 in the per protocol analysis. The primary efficacy endpoint was the number of periods with no leakage for 4 h after dosing. Women were instructed to take the drug at a time of their choosing, but >/= 4 h before bedtime. Secondary efficacy variables included the time to first void or incontinence episode, volume leaked per incontinence episode, total volume voided and number of periods with no leakage. All measurements were made over 7 days on desmopressin and 3 days on placebo.

There was a higher mean (sd) incidence of periods with no leakage in the first 4 h on desmopressin, at 62 (35)%, than on placebo, at 48 (40)%, and during the first 8 h, at 55 (37)% vs 40 (41)%. There was also a higher frequency of dry days on desmopressin than on placebo; 36% of patients had no leakage on virtually all treatment days (6 or 7) for 4 h after dosing. At 4-8 h the incidence of periods with no leakage on desmopressin was 68 (35)% vs 63 (41)% on placebo, and thereafter the incidence was similar. The time from dosing to first incontinence episode was longer on desmopressin, at 6.3 (2.5) h, vs 5.2 (3.3) h, whilst the volume leaked per incontinence episode was lower on desmopressin than placebo. The total volume voided was consistently lower on desmopressin, at 1180 (58) mL vs 1375 (57) mL, over the 24-h period after administration. There were no serious or severe adverse events reported. Seven women (11%) withdrew from the study, of whom five did not attend for the final visit and two (3%) because of mild adverse events.

The results of this exploratory study suggest that desmopressin is an effective and safe treatment in women with daytime urinary incontinence, and allows them to choose when they need treatment, thus improving motivation, which may aid compliance with therapy.

Autonomic nervous system (ANS) dysfunction is common in Parkinson's disease (PD), affects 70% to 80% of patients, and causes significant morbidity and discomfort. Autonomic nervous system dysfunction symptoms in PD include sexual dysfunction, swallowing and gastrointestinal disorders, bowel and bladder abnormalities, sleep disturbances, and derangements of cardiovascular regulation, particularly, orthostatic hypotension. Autonomic nervous system dysfunction in PD may be caused by an underlying degenerative process that affects the autonomic ganglia, brainstem nuclei, and hypothalamic nuclei. Anti-parkinsonian medications can cause or worsen symptoms of ANS dysfunction. The care of a PD patient with ANS dysfunction relies on its recognition and directed treatment, including coordinated care between the neurologist and appropriate subspecialist. Pharmacotherapy may be useful to treat orthostasis, gastrointestinal, urinary, and sexual dysfunction.

Frequent episodes of nocturnal voiding disturb the sleep and well-being of women. The prevalence of nocturia is more common in parous women and shows a linear increase with age, occurring in more than 50% of women > or =80 years old. Nocturia has a multifactorial origin that develops through a pathophysiologic mechanism of nocturnal polyuria or low functional bladder capacity or through a combination of both. Nocturia is also one of the most bothersome lower urinary tract symptoms and has a significant impact on quality of life. However, most women accept symptoms of nocturia as part of the aging process and few seek medical help. Treatments for nocturia (behavior modification and pharmacologic treatment) are effective in many cases, although it is important to tailor treatment to the underlying pathophysiology. This review discusses the impact of nocturia on women and reviews the current situation regarding the definition, prevalence, diagnosis, and treatment of this condition in this patient population.

The majority of patients with multiple sclerosis (MS) experience genitourinary and bowel dysfunction over the course of their illness. Lower extremity pyramidal signs are excellent predictors of concurrent bladder dysfunction. Constipation is the most common bowel dysfunction, which results from a range of causes including pelvic floor spasticity, decreased gastro-colic reflex, inadequate hydration, medications, immobility, poor physical conditioning, and weak abdominal muscles. Despite the advent of new therapeutic modalities, the physician and patient commonly overlook sexual dysfunction. A detailed history of the patient is crucial to determine the cause of the dysfunction. Fatigue, pain, mood disorders, spasticity, bowel, and bladder dysfunction can all interfere with normal sexual functioning, and these subjects should be explored in detail in order to plan for proper treatment. Integrated treatment plans, often in conjunction with an urologist, can lead to amelioration of symptoms.

Drugs used for treatment of urinary incontinence may act on the central nervous system (CNS) or peripherally. Few drugs with a defined CNS site of action are available for treatment of urine storage disorders; most of those currently used have a peripheral site of action. To treat bladder overactivity associated with urgency and urge incontinence, antimuscarinic drugs, alpha-adrenoceptor antagonists, beta-adrenoceptor agonists, prostaglandin synthesis inhibitors, and several other agents most often developed for non-urological indications, are employed. Current treatment is based on the use of antimuscarinic drugs, and oxybutynin is, despite a high incidence of side-effects, the gold standard. Pharmacological treatment of stress incontinence has had limited success, and only alpha-adrenoceptor agonists, with and without combination with oestrogens have had a documented effect. New drugs, specifically directed at treatment of urine storage disorders, are desirable.

The benefit of desmopressin (DDAVP) in the treatment of the urinary symptoms of multiple sclerosis has until now only been shown in short crossover studies of up to 6 weeks. We report 19 patients who have used the drug for an average of 2 years and 4 months, 18 of whom confirmed continued dramatic benefit without any obvious change in dosage used or efficacy and with few side effects. Ten of the 19 patients had also used DDAVP during daytime for special occasions with notable success. This is the first study to suggest that DDAVP is safe and effective in long term use in MS.

The aging process, behavioural habits and a multitude of pathological conditions are the main contributors to the development of nocturia in the elderly. Age-related physiological changes can alter the regular pattern of urine excretion and lead to increased nocturnal frequency of voiding. In addition, aging is associated with anatomical and physiological changes of the urinary tract itself that predispose to increased urinary frequency without affecting urine volume. Several urinary and extra-urinary tract conditions may have nocturia as a prominent symptom. These conditions can be grouped as those associated with bladder overactivity, bladder outlet obstruction, bladder hypotonicity and an increased urine volume. A detailed assessment that gathers clues from the medical history, physical examination and laboratory is of utmost importance in identifying the specific causes. Overactive bladder can be idiopathic or associated with different triggers such as UTI, bladder stones, bladder tumours and CNS diseases that disrupt the normal inhibitory signals to the bladder. It may be cured by the successful elimination of the trigger conditions. Therapeutic modalities include behavioural therapies with scheduled voiding, anticholinergic drugs and in women the use of transvaginal electrical stimulation. Benign prostatic hyperplasia is the most common cause of bladder outlet obstruction in men. Different drug classes (e.g. peripheral alpha-adrenoceptor blockers and 5 alpha-reductase inhibitors) are now available for the treatment of mild to moderate symptoms. Surgery is reserved for patients with severe symptoms or with complications, with new and less invasive surgical techniques being preferred. Bladder hypotonicity is usually caused by peripheral neuropathies, spinal cord lesions and the indiscriminate use of drugs with anticholinergic actions. Treatment involves discontinuation of implicated drugs, short term use of cholinergic drugs and urinary catheterisation. Increased urine volumes and nocturia are frequently seen in hyperosmolar and oedematous states. Excessive ingestion of fluids, caffeinated or alcoholic beverages are habits that commonly produce nocturia. Although more definitive studies are awaited, low dose loop diuretics given a few hours prior to bedtime and desmopressin nasal spray or tablets may be useful alternatives for the control of nocturic symptoms in elderly patients with nocturnal polyuria syndrome. Whenever nocturia is present, clinicians should try to identify its causes by means of a thorough history, physical examination and pertinent complimentary tests. Once the specific cause or causes are found, most cases can be satisfactorily managed with behavioural, pharmacological or surgical therapies.

To report our experience of the use of desmopressin to improve nocturnal dryness in patients who have undergone a staged reconstruction of the exstrophy-epispadias complex (EEC), who although continent by day, have nocturnal incontinence because their nocturnal urinary output exceeds their bladder capacity.

Seven children (aged 8-12 years) who had undergone a staged reconstruction for EEC (six with classical bladder exstrophy, one with incontinent epispadias) were treated with intranasal desmopressin for persistent nocturnal incontinence despite daytime dryness. Previous additional procedures for continence had been self-augmentation in one and periurethral collagen injection in three others. The criteria for inclusion in the study were: normal renal function, no upper tract deterioration, no urinary tract infections, spontaneous voiding during the day with dry intervals between micturitions, a postvoid residual volume of <10% of bladder capacity and night-time incontinence for 7 nights/week. Desmopressin was administered at bedtime at increasing dosages from 10 to 30 microg until effective. Body weight, arterial blood pressure, and serum electrolytes were measured, and all patients assessed using renal ultrasonography, a voiding diary and a nocturnal pad-test.

Desmopressin at doses of 10-30 microg was successful in keeping all the patients dry. The nocturnal urinary output was decreased so that it did not exceed bladder capacity. There was only one minor side-effect (nose bleeding).

In selected patients with EEC, desmopressin is effective in improving nocturnal dryness, with no significant side-effects.

An overview of the current concepts of the neurological control of the bladder is given, based on laboratory experiments and PET scanning studies in human subjects. This is followed by a description of the various causes of the neurogenic bladder, discussed in a hierarchical order starting with cortical lesions and descending through the basal ganglia and brainstem, spinal cord, conus and cauda equina to disorders of peripheral innervation. Then follows a description of the condition of isolated urinary retention in young women. The article concludes with a review of the methods available for treating neurogenic bladder disorders. These are largely medical but brief mention of appropriate surgical procedures is made.

To assess whether desmopressin (1-desamino 8-d-arginine vasopressin) is safe and effective in the treatment of nocturnal polyuria in elderly men.

Twenty men (age 52-80 years) complaining of nocturia were found to have nocturnal polyuria, determined from frequency-volume charts and defined as the production of >33% of the 24 h urine volume overnight, averaged over a 1-week period. In a double-blind study of cross-over design, a 1-week placebo run-in period was followed by two 2-week periods of placebo or 20 microg intranasal desmopressin, and ended with an open 2-week treatment period with 40 microg desmopressin.

Desmopressin caused a significant reduction in nocturnal urine volume and the percentage of urine passed at night, but the reduction in nocturnal frequency was only significant during treatment with 40 microg desmopressin. Four patients on desmopressin experienced side-effects, three of which were thought to be due to fluid retention.

Desmopressin is an effective treatment for nocturnal polyuria in some elderly men. However, it can cause fluid retention and should not be given to patients with cardiac failure. Those undergoing treatment must be closely monitored.

To evaluate the decrease in nocturnal diuresis, nocturnal polyuria and the safety of oral desmopressin in elderly subjects with nocturia.

After being identified using a population-based questionnaire, subjects were included in the study if they; (i) were healthy and free from medication with possible influence on the diuresis or voiding pattern; (ii) had an increased nocturnal frequency (>/=2 nocturnal voids/night, as reported before screening); (iii) had a nocturnal urinary output of >/=0.9 mL/min; (iv) completed and responded to an initial dose-titration study. Twelve men and five women (mean age 67.7 years, sd 4.6 years) met these criteria and were treated with oral desmopressin or placebo at bedtime for 2 weeks on each medication in a randomized, double-blind, crossover design.

Subjects treated with desmopressin had a significantly reduced nocturnal diuresis of 0.59 mL/min compared with those on placebo (95% confidence interval, CI, 0.33-0.85). The 24-h diuresis was unaffected by desmopressin treatment. Patients treated with desmopressin had fewer micturitions at night than had those on placebo (1.1 and 1.7, respectively; P<0.001; mean difference=0.59; 95% CI, 0.32-0.85). The reduction in nocturnal diuresis was dependent on the baseline level of night-time diuresis (r=0.886; r2=0.785; P<0.0001) and the nocturnal part of the baseline 24 h-diuresis (r=0.708; r2=0.502; P<0.001). After desmopressin treatment was withdrawn, diuresis returned to the levels before treatment. The time from falling asleep to first awakening was improved by 1.4 h in patients treated with desmopressin. There was no change in body weight or ankle circumference during desmopressin treatment. Overall, the treatment was well tolerated and no serious adverse events were observed.

Desmopressin was effective in reducing nocturnal diuresis and nocturnal voids in polyuric elderly subjects, with no significant adverse events or inconvenience to the patient. The length of uninterrupted sleep was also improved.

To evaluate the decrease in nocturnal polyuria and the tolerability of three different doses of oral desmopressin in elderly subjects.

Subjects were included in the study if they; (i) were healthy and free from medication with possible influence on their diuresis or voiding pattern: (ii) had an increased nocturnal frequency (> or = 2 nocturnal voids, as reported in the pre-screening period); and (iii) had a nocturnal urinary output of > or = 0.9 mL/min. Seventeen men and six women (mean age 68.1, SD 4.7 years) met these criteria and were treated with 0.1, 0.2 and 0.4 mg oral desmopressin given at bedtime, each dose taken for one week on three consecutive weeks.

The mean (SD) nocturnal diuresis before treatment was 1.6 (0.7) mL/min, which decreased significantly to 1.1 (0.4) mL/min when 0.1 mg desmopressin was given. A dose of 0.2 mg desmopressin resulted in a further small decrease in the nocturnal diuresis to 0.9 (0.4) mL/min, whereas the 0.4 mg dose produced no additional effect. The reduction in nocturnal diuresis occurred almost exclusively in the group with a nocturnal urinary output of > or =1.3 mL/min. After treatment, diuresis returned to pretreatment levels. There was no change in body weight or in ankle circumference during desmopressin treatment and no serious adverse effects were observed.

Desmopressin reduces nocturnal diuresis in polyuric elderly subjects and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose-dependent way.

Multiple sclerosis (MS) is an immunologically mediated disorder in which inflammation and demyelination of the central nervous system white matter are prominent features, resulting in various neurological signs and symptoms. In most patients, the course of the disease is initially characterised by relapses and remissions. In patients with chronic disease there is a tendency towards a gradually progressive disease course. MS relapses can best be treated with a course of high dose intravenous methylprednisolone. In ambulatory patients with relapsing remitting MS, partial prevention of relapses can be achieved by the use of interferon-beta-1a or -1b, whereas there is (as yet less convincing) evidence that glatiramer acetate (copolymer-1) might also be effective. At this time, there is no proof that these drugs are effective in patients with progressive MS, although trial results are expected to be available soon. In patients with rapidly progressive disease, it might be worth considering the effect of methotrexate. Future treatment options include new strategies to interfere with disease-relevant, specific or nonspecific immune mechanisms as well as drugs that might promote remyelination. In spite of the advances that have been made over the past few years, symptomatic treatment, including a multidisciplinary rehabilitation approach, remains the mainstay of treatment of the majority of MS patients.