Jalesh Panicker

A UK consensus on the management of the bladder in multiple sclerosis

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients’ continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.

Lower urinary tract dysfunction in the neurological patient: clinical assessment and management

Lower urinary tract (LUT) dysfunction is a common sequela of neurological disease, resulting in symptoms that have a pronounced effect on quality of life. The site and nature of the neurological lesion affect the pattern of dysfunction. The risk of developing upper urinary tract damage and renal failure is much lower in patients with slowly progressive non-traumatic neurological disorders than in those with spinal cord injury or spina bifida; this difference in morbidity is taken into account in the development of appropriate management algorithms. Clinical assessment might include tests such as uroflowmetry, post-void residual volume measurement, renal ultrasound, (video-)urodynamics, neurophysiology, and urethrocystoscopy, depending on the indication. Incomplete bladder emptying is most often managed by intermittent catheterisation, and storage dysfunction by antimuscarinic drugs. Intradetrusor injections of onabotulinumtoxinA have transformed the management of neurogenic detrusor overactivity. Neuromodulation offers promise for managing both storage and voiding dysfunction. An individualised, patient-tailored approach is required for the management of LUT dysfunction associated with neurological disorders.

Suburothelial Myofibroblasts in the Human Overactive Bladder and the Effect of Botulinum Neurotoxin Type A Treatment

BACKGROUND An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO). OBJECTIVE To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA). DESIGN, SETTING, AND PARTICIPANTS Patients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064. INTERVENTIONS Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit. MEASUREMENTS Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes). RESULTS AND LIMITATIONS Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment. CONCLUSIONS Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.

Long-Term Effect on Quality of Life of Repeat Detrusor Injections of Botulinum Neurotoxin-A for Detrusor Overactivity in Patients With Multiple Sclerosis

PURPOSE We studied the effect of repeat detrusor botulinum neurotoxin type A injections on urinary symptoms, health and quality of life in patients with refractory neurogenic detrusor overactivity secondary to multiple sclerosis. MATERIALS AND METHODS This was a prospective, open label, single center study in 137 patients with multiple sclerosis treated with detrusor injections of botulinum neurotoxin type A with observations made from 2002 to 2009. A minimally invasive outpatient technique was used for injection. Patients were asked to contact the department if and when they required repeat treatment. Recurrent detrusor overactivity was then identified on urodynamics. The primary outcomes measured were the change in symptoms and quality of life, as assessed by the Urogenital Distress Inventory, Incontinence Impact Questionnaire and EuroQol-5 Dimensions questionnaires (www.ion.ucl.ac.uk/departments/repair/themes/uroneurology) before and 4 weeks after botulinum treatment. Continence status, the need for clean intermittent self-catheterization before and after injections, and interinjection intervals were also analyzed. RESULTS Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire 7 scores showed considerable improvement 4 weeks after each treatment even when repeated 6 times. Almost all patients relied on clean intermittent self-catheterization after treatment. Before the first treatment 83% of patients were incontinent but 4 weeks after the first treatment 76% (104 of 137) became completely dry. This efficacy was sustained with repeat injections. The median interval between re-treatments remained constant at 12 to 13 months. CONCLUSIONS Repeated detrusor botulinum neurotoxin type A injections for refractory neurogenic detrusor overactivity in patients with multiple sclerosis have a consistent effect on bladder control, resulting in sustained improvement in quality of life.

What a patient with refractory idiopathic detrusor overactivity should know about botulinum neurotoxin type a injection.

PURPOSE We documented the effects of intradetrusor injections of botulinum neurotoxin type A (Botox(R)) for refractory idiopathic detrusor overactivity so that prospective patients maybe properly informed about possible improvement in quality of life, the duration of interinjection intervals and the risk of clean intermittent self-catheterization. MATERIALS AND METHODS A total of 81 consecutive patients with refractory idiopathic detrusor overactivity treated with intradetrusor injections of 200 U botulinum neurotoxin type A at 20 sites per injection course were evaluated in this prospective, nonrandomized, open label cohort study. The primary outcome was changes in quality of life, as assessed by the short form of the Urogenital Distress Inventory and the Incontinence Impact Questionnaire before and after treatment. Secondary outcomes were the interinjection interval and the need for clean intermittent self-catheterization. RESULTS After intradetrusor botulinum neurotoxin type A injections there was significant improvement in quality of life, which was sustained after repeat injections. Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire scores decreased from 56 to 26 and 59 to 21 after injection 1 in 81 patients, from 52 to 30 and 51 to 24 after injection 2 in 24, from 40 to 19 and 43 to 17 after injection 3 in 13, from 44 to 17 and 61 to 15 after injection 4 in 6 and from 51 to 17 and 63 to 14 after injection 5 in 4, respectively. The median interinjection interval was 15, 12, 14 and 13 months between injections 1 and 2, 2 and 3, 3 and 4, and 4 and 5, respectively. Considering a post-void residual urine of greater than 100 ml with lower urinary tract symptoms as the indication for clean intermittent self-catheterization, the overall clean intermittent self-catheterization rate after treatment was 43%. CONCLUSIONS Intradetrusor botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity significantly improved quality of life. This effect was sustained after repeat injection. More than 2 of 5 patients with refractory idiopathic detrusor overactivity required clean intermittent self-catheterization after botulinum neurotoxin type A injections and all prospective patients should be informed about this.

Sexual dysfunction in multiple sclerosis

Multiple sclerosis is a chronic disease that commonly affects young adults who may be sexually active. Sexual dysfunction is a significant, but often underestimated, symptom of multiple sclerosis, affecting 50–90% of men and 40–80% of women. The types of sexual dysfunction can be categorized in terms of the normal sexual response cycle: sexual interest/desire dysfunction (reduced libido), sexual arousal dysfunction (including erectile dysfunction) and ejaculatory and orgasmic dysfunction. Sexual dysfunction may not only be due to lesions affecting the neural pathways involved in physiological function (primary dysfunction), but also result from general physical disabilities (secondary dysfunction) or psychological and emotional issues (tertiary dysfunction). Comprehensive management should address all these possible contributing problems. Specific pharmacotherapy is only currently available for erectile dysfunction. This review summarizes the available information about sexual dysfunction in men and women with multiple sclerosis.

Clean Intermittent Self-catheterization After Botulinum Neurotoxin Type A Injections: Short-term Effect on Quality of Life

OBJECTIVE: To investigate the hypothesis that the need for clean intermittent self-catheterization after botulinum neurotoxin type A injections is outweighed by the efficacy of this treatment, so that clean intermittent self-catheterization is not a burden for patients with refractory idiopathic detrusor overactivity. METHODS: Women undergoing intradetrusor injections of 200 units botulinum neurotoxin type A for refractory idiopathic detrusor overactivity were evaluated prospectively. Clean intermittent self-catheterization was discussed with all patients and its possible need after botulinum neurotoxin type A treatment. As indicator of quality of life, lower urinary tract symptom distress and effect on daily activities were assessed using the validated Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) before and 4 weeks after receiving botulinum neurotoxin type A injections. RESULTS: Mean age of the 65 women was 51 years, and all voided spontaneously before botulinum neurotoxin type A injections. After botulinum neurotoxin type A treatment, 28 (43%) required clean intermittent self-catheterization. Mean UDI-6 and IIQ-7 scores reduced from 61 to 33 (P<.001) and 62 to 30 (P<.001) in women performing clean intermittent self-catheterization and from 60 to 28 (P<.001) and 64 to 25 (P<.001) in those who did not, respectively. Comparison of quality of life in women performing clean intermittent self-catheterization and in those who did not revealed no significant differences before and after botulinum neurotoxin type A treatment. CONCLUSION: Clean intermittent self-catheterization after botulinum neurotoxin type A intradetrusor injections did not impair quality of life in appropriately informed and selected women in the short term. All patients should be informed of the potential need for clean intermittent self-catheterization after botulinum neurotoxin type A injections, and a willingness to do so should be a prerequisite for this still unlicensed off-label treatment. LEVEL OF EVIDENCE: III

Ensuring patient adherence to clean intermittent self-catheterization.

Patient performance of clean intermittent self-catheterization is a crucial component of the management of incomplete bladder emptying, which can arise from a variety of conditions. This allows patients to have more control over their bladder emptying, and avoids the inconveniences that come with an indwelling urethral catheter. There are, however, barriers that patients face when performing this task which may ultimately limit adherence. In this article, these barriers are discussed in more detail with potential solutions to counter them.

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned.

Rehabilitation in Practice: Neurogenic lower urinary tract dysfunction and its management

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is ‘the trainee consistent demonstrates a knowledge of the pathophysiology of various specific impairments including bladder dysfunction’ and ‘management approaches for specific impairments including bladder dysfunction’. The lower urinary tract (bladder and urethra) has two roles: storage of urine and emptying at appropriate times. The optimal and coordinated activity of the lower urinary tract is subject to a complex neural control which involves all levels of the nervous system, from cortex to peripheral innervation. The complexity of the neural control of lower urinary tract explains the high prevalence of urinary disturbances in neurologic disease. Information obtained from history taking and supplemented by use of a bladder diary forms the cornerstone of evaluation. Ultrasonography is used to assess the degree of incomplete bladder emptying, and for assessing the upper tracts. Urodynamic tests, with or without simultaneous fluoroscopic monitoring, assess detrusor and bladder outlet function and give fundamental information about detrusor pressure and thus the risk factor for upper tract damage. Impaired emptying is most often managed by clean intermittent self-catheterization and this should be initiated if the post-void residual urine is greater than 100 mL or exceeds one third of bladder capacity, or rarely if spontaneous voiding is dangerous due to high detrusor pressure. Storage symptoms are most often managed using antimuscarinic medications. Other options include desmopressin to reduce urine output or intradetrusor injection of botulinum toxin type A to reduce detrusor overactivity. Understanding of the underlying mechanism of lower urinary tract dysfunction is crucial for effective management.