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The management of female voiding dysfunction: Fowler's syndrome -- a contemporary update.

PURPOSE OF REVIEW: Several aspects of voiding dysfunction in women remain under investigation, including standardization of the diagnosis and management of bladder outflow obstruction. This article describes a specific cause of urinary retention in young women, associated with a failure of urethral sphincter relaxation, and a treatment option that can restore voiding in this group of patients - sacral nerve electrical stimulation therapy. Recently there have been advances in the stimulator implantation technique, as well as in our appreciation of its mechanism of action. RECENT FINDINGS: Advances include the use of ancillary investigations such as urethral function tests as well as better understanding of the clinical profile of these patients. Improvements in the surgical technique include better methods of lead fixation and a less invasive surgical approach. Research suggests the action of neuromodulation is on the afferent pathway, though it remains to be shown whether this is at a spinal or supraspinal level. It is likely that sacral nerve stimulation has an indirect modulatory effect on detrusor contractility rather than a direct effect on the sphincter. SUMMARY: Experience of sacral nerve stimulation has increased over the past few years, and its application is expanding to other clinical domains. This knowledge has helped improve the therapy, which is particularly effective in the treatment of women with urinary retention. Although how it works is still not fully understood, this is something that is being addressed by ongoing research.

Adrenergic alpha-Agonists↗

Buttock placement of the implantable pulse generator: a new implantation technique for sacral neuromodulation--a multicenter study.

OBJECTIVE: In the standard operation procedure for sacral neuromodulation, the implantable pulse generator (IPG) is implanted in a subcutaneous pocket at the lower part of the anterior abdominal wall. This procedure requires a long operation time and three incisions. With the IPG in the abdominal wall, some patients complain of displacement or pain at the IPG site postoperatively. By modifying the technique of placement of the IPG, these disadvantages are overcome. METHODS: Between August 1999 and July 2000, 39 patients underwent a buttock implant of the IPG. In 2 of these patients the position of the IPG was changed from abdominal region to the buttock. During follow-up, complications concerning the operation and location of the IPG were compared to the published literature. RESULTS: Operation time is reduced in all patients by approximately 1 h. No repositioning of the patient is required during surgery. Only a short subcutaneous tunnel is required to connect the lead to the IPG. Pain at the level of the IPG was noted in 10% of the patients, which needed no further treatment. No infections were seen and the IPG did not displace postoperatively. CONCLUSION: Buttock placement of the IPG in sacral nerve stimulation leads to shorter operation time; only two incisions are needed instead of three and a shorter subcutaneous tunnel is needed. Using this technique there are less complications and a lower re-operation rate.

Adult↗

Sacral nerve neuromodulation for the treatment of lower bowel motility disorders.

INTRODUCTION: Incontinence and constipation are common and cause a high degree of physical, social and psychological impairment. Maximal conservative therapy may improve some patients but many remain symptomatic. Surgical options are often unsatisfactory, with variable result and further options are limited. Sacral nerve stimulation uses electrical stimulation applied to the sacral nerves, eliciting a physiological effect on the lower bowel, anal sphincter and pelvic floor, resulting in clinical benefit. The objective of this study was to investigate whether sacral nerve neuromodulation can improve patients with disorders of bowel motility, when current maximal treatment has failed and to investigate the underlying physiological mechanism of action. RESULTS: Incontinence: Nineteen patients, age 58 years (range, 37-71 years), with resistant incontinence for 6 years (range, 2-21 years) underwent stimulation. Continence improved in all at 24 months (range, 3-60 months), fourteen fully continent. Incontinent episodes decreased; 12 (range, 2-30) versus 0 (range, 0-4), P < 0.001. Urgency (P < 0.01) and quality of life improved (P < 0.05). Anal squeeze pressure (P = 0.001) and rectal sensation (P < 0.01) improved. Constipation: Four women, (aged 27-36 years) with resistant idiopathic constipation for 8-32 years underwent the first worldwide implants. Symptoms improved in all with temporary, and in three with permanent, stimulation at 8 months (range, 1-11 months). Bowel frequency increased: 1-5 versus 6-28 evacuations/3-weeks. Symptom scores and quality of life improved. Placebo effect: A double-blind, cross-over study was performed to examine placebo effect and efficacy. Once stimulation was removed, in a blinded manner, symptoms, physiological parameters and quality of life measures rapidly returned to baseline levels. Autonomic neuromodulation: Sixteen patients, median age 59 years (range, 38-71 years), were studied at 27 months (range, 2-62 years) using laser Doppler flowmetry. Chronic stimulation was at 2.8 V (range, 0.3-3.9 V). Median flux differed between none and chronic stimulation (P = 0.001). Step-wise increments caused an immediate, dose-dependent rise in flux (P < 0.0001) up to 1.0 V. CONCLUSIONS: This research provides strong evidence that sacral nerve stimulation can improve patients with resistant incontinence and shows proof-of-concept for the treatment of constipation. The effect is unlikely to be due to placebo and the mechanism is rapidly reversible and involves a dose-dependent effect on the autonomic nerves.

Adult↗

Applications of neuromodulation of the lower urinary tract in female urology.

Neuromodulation is becoming part of clinical armamentarium for treatment of a variety of lower urinary tract conditions in female urology. Its increased usage stems from need of patients who have exhausted all other therapeutic options for their complex and poorly understood lower urinary tract disorders. Currently neuromodulation may consist of the use of sacral nerve stimulation (SNS) and injectable therapies. Herein, we will discuss the background and development of SNS, its current indications, methods of patient selection and will review the results of the recent published literature on SNS. In addition, we will discuss some of the newer developments in SNS such as Bion device and the future direction in integration of SNS in female urology.

Clinical Trials as Topic↗

Sacral nerve stimulation.

The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

Electric Stimulation Therapy↗

Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence.

OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.

Adult↗

Sacral rhizotomies and electrical bladder stimulation in spinal cord injury. 2. Cost-effectiveness and quality of life analysis. Dutch Study Group on Sacral Anterior Root Stimulation.

OBJECTIVES: To present a cost-effectiveness analysis of sacral rhizotomies and electrical bladder stimulation compared with conventional care of neurogenic bladder dysfunction in patients with spinal cord injury. METHODS: During a 3-year inclusion period, data on costs and quality of life before the intervention were collected to describe conventional care. Data on the pre-implantation period, the implantation and a follow-up period of 2 years were collected following a strict protocol simultaneous with medical and urodynamic data and were used to calculate the costs and effects on quality of life of the implantation of the stimulator. RESULTS: Between June 1991 and June 1994, 52 patients with complete cervical or thoracic spinal cord lesions underwent sacral posterior rhizotomies and implantation of a Finetech-Brindley sacral anterior root stimulator. Although the initial costs of sacral anterior root stimulation are high, they are earned back in this series in about 8 years after the implantation. General indicators of the quality of life show no significant changes after the implantation. Factors related to psychological well-being and the patients' satisfaction with the emptying of the bladder increased significantly whereas the experienced problems of micturition and incontinence all decreased significantly. CONCLUSION: Sacral rhizotomies and electrical bladder stimulation make a cost-effective method of treatment of lower urinary tract dysfunction in patients with spinal cord injury. Considerable savings on health care costs are possible in the long run with simultaneous positive effects on aspects of health status.

Adolescent↗

Distribution of lumbar and sacral afferent axons in submucosa of cat urinary bladder.

Lumbar and sacral afferent axons in the submucosa of the urinary bladder were recognized by degeneration in seven cats subjected to spinal ganglionectomies. Of 2,935 observed terminating axon profiles, 145 were found degenerating. Lumber afferent axons were 3.7 times more numerous than sacral afferent axons in the submucosa, a reversal of the ratio reported for the muscle coat of the bladder. Sacral afferent axons were evenly distributed to different regions of the bladder, but lumbar afferents were concentrated in the bladder neck. Apparent afferent endings in the submucosa of the urinary bladder were principally free nerve endings. Synaptic vesicles were found in 57% of observed terminating axon profiles. The bladder neck had more terminating axon profiles of all kinds than other regions of the urinary bladder.

Animals↗

Neuromodulation of sacral nerves for incontinence and voiding dysfunctions. Clinical results and complications.

Neuromodulation of sacral nerves is a new form of treatment for patients with refractory voiding dysfunctions such as incontinence, retention and chronic pelvic pain. Electrical stimulation of S3 activates the pelvic floor and modulates innervation of the bladder, sphincter and pelvic floor, restoring the balance and coordination in sacral reflexes. 19 of 23 patients with an implanted neuroprosthesis for neuromodulation have a more than 50% improvement in their main symptoms after a median follow-up of 12 months. In urge-incontinent patients the number of leakings decreased from 7.4 to 1.5/day, and the functional capacity increased from 135 to 227 ml.

Abdominal Pain↗

Feasibility of inducing micturition through chronic stimulation of sacral roots.

Past attempts at inducing micturition in paraplegics by electric stimulation of the spinal cord micturition center have been generally unsuccessful. Failure has most often resulted from inability to separate the response of the detrusor from that of the sphincter. Because the sacral nerves provide some organizational specificity over the spinal cord and are practically suited to chronic stimulation, experiments were carried out in dogs to find out whether or not stimulation of these roots could induce micturition. Results of acute dog studies did suggest that micturition might effectively be performed by stimulation of the ventral root of the sacral nerve having the greatest detrusor representation. Specificity of bladder response was improved by dividing somatic fibers peripherally. Selected division of somatic fibers from the sacral root stimulated was compared with complete pudendal neurotomy. (The former procedure has the advantage of preserving perineal sensation.) The principles learned from the acute studies were then applied to "chronic" dogs--5 paraplegic and 1 normal. Effective voiding was achieved on a long-term basis. Over-all results were very encouraging. Further research is necessary before application of this technique to humans can be considered.

Animals↗

FES for bladder: direct or indirect means?

Efforts to restore function to the neurologically disabled lower urinary tract by direct electrical stimulation of the bladder wall have met with only very limited success. This has been due to pain and cocontraction of bladder outlet mechanisms caused by presumed spread of the large currents required to effectively directly stimulate the detrusor muscle. Stimulation at the four anatomical sites of the sacral neural outflow on the other hand has been more successful. Conus medullaris stimulation has resulted in "good results" in just over half of the 28 patients so treated. Acceptance of this technique has been limited by the poor selectivity of the intramedullary electrodes in stimulating only the target motor neurons and the resultant clinical problems with the consequent stimulus current spread. Sacral anterior root stimulation has been used in at least 88 patients with generally good results. Cocontraction of the detrusor and external urethral sphincter are circumvented by the use of an intermittent pattern of stimulation. The primary disadvantage of this technique is the obligatory placement of the electrodes within the cerebrospinal fluid compartment. Clinical experience with stimulation of the extradural sacral mixed nerves is limited. Experimental studies indicate that success with this technique requires dorsal rhizotomy and pudendal neurotomy. Preliminary clinical experience suggests that these surgical manipulations may not be necessary for a successful outcome. The literature on clinical application of pelvic nerve stimulation is too limited for detailed comment on this technique. A definitive technique for restoration of bladder function by electrical stimulation remains to be developed.

Electric Stimulation Therapy↗

[Functional anatomy of the pelvic veins in women].

Pelvic veins and lower extremities veins form a functional unit resulting in the interaction of their pathology. The intrapelvic venous system consists of two independent networks, under physiological conditions: the parietal and the visceral networks. The main collectors are the internal iliac veins, the ovarian superior rectal veins. The original venous plexi, located in the sub-peritoneal pelvic connective tissue, remain open because of the adhesion of their wall to the parietal pelvic fascia. The parietal venous network, abundant and supplied with valves, includes the retro-public and sacral plexi. The usual venous drainage is encouraged by abundant anastomoses, the decrease or even the absence of valves and the abdominal pressure. When this pressure increases, especially during walking, this encourages pelvic drainage. Occasional venous drainage is observed in case of obstruction of the usual collectors. Anatomical obstacles to the drainage, besides thrombosis and tumors, are essentially: compression of the left common iliac vein by the right common iliac artery, and direct compression of the inferior vena cava by the uterus during pregnancy which compresses it against the spine. It is responsible for gravidic postural shock, and an increased abdominal pressure, exceeding 20 mmHg. The main supply pathways are the ovarian veins and the vertebral plexi. This large, low-pressure avalvular plexus may function easily in both directions caudo-cranial and cranio-caudal. The relationship of this plexus with the roots of the sciatic nerve explain certain sciaticas during pregnancy. Dilatation of the ovarian veins during pregnancy cause a so called syndrome of the ovarian vein. Various venous compressions during pregnancy are responsible for some hematurias, increased collateral abdominal circulation, and turgescent haemorrhoids and vulvar varicose veins.

Abdomen↗

Sacral root stimulation in controlled micturition. Peripheral somatic neurotomy and stimulated voiding.

Stimulation of the sacral ventral roots with the largest detrusor representation was found to be moderately successful for bladder emptying in acute canine experiments. However, removal of spinal reflexes arising from sacral root stimulation did not eliminate sphincteric resistance. For that reason ventral roots were stimulated after peripheral somatic neurotomy. Unilateral pudendal nerve sectioning was compared with selective sectioning of the somatic fibers of S2, the root with the greatest detrusor representation in canines. Both were equally effective in significantly reducing outlet resistance. Selective nerve section has one advantage: it preserves more of the nerve pathways involved in reflexogenic erection.

Animals↗

Ultrastructural analysis of enkephalinergic terminals in parasympathetic ganglia innervating the urinary bladder of the cat.

Leucine enkephalin immunoreactivity was identified in axons and varicosities in parasympathetic ganglia located in the pelvic plexus and on the surface of the urinary bladder of the cat. Electron microscopic immunohistochemical studies revealed that varicosities containing leucine enkephalin exhibited large dense core vesicles and small, clear, spherical vesicles, which were similar to those found in cholinergic terminals. Leucine enkephalin immunoreactivity was primarily associated with large dense core vesicles. The varicosities formed axodendritic and axosomatic synapses with principal ganglion cells. Axoaxonic synapses were not detected. Some axosomatic enkephalinergic synapses were detected embedded within or invaginating the principal ganglion cells. Varicosities containing flattened and/or small dense core vesicles did not exhibit enkephalin immunoreactivity. Bladder ganglion cells identified by retrograde HRP tracing from the urinary bladder exhibited similar leucine enkephalinergic synapses. These observations, coupled with previous reports that leucine enkephalin is present in sacral preganglionic neurons and released by preganglionic nerve stimulation, suggest that leucine enkephalin and acetylcholine are cotransmitters stored and released from the same nerve terminals in bladder parasympathetic ganglia.

Animals↗

Multiple peripheral nerve compressions related to malignantly transformed hereditary multiple exostoses.

Autosomal dominantly transmitted hereditary multiple exostoses is an uncommon disorder consisting of multiple projections of bone capped by cartilage. The lesions are most numerous in the metaphyses of long bones but may appear on flat bones. Sarcomatous transformation occurs in 1-25% of patients. We report a 33-year-old man with sciatica, previously diagnosed as hereditary multiple exostoses, presenting with multiple peripheral nerve compressions. Electrodiagnostic studies showed profound axon-loss multiple neuropathies involving the sciatic, superior gluteal, and inferior gluteal nerves. Magnetic resonance imaging of the left pelvis showed a large mass in the sacral area that was suggestive of a chondrosarcoma. An open intralesional excision biopsy confirmed chondrosarcoma transformed from chondromatosis. Excision of the lesion was effective in eliminating the impingement of nerves and retarding progressive osseous growth. We suggest that malignant transformation be suspected in cases with focal compression neuropathy of patients known to have multiple exostoses. Osteochondroma as a possible cause for compression neuropathy is discussed.

Adult↗

Long-term follow-up of selective sacral neurectomy.

Between 1976 and 1981, 22 patients underwent selective, complete sacral root section as a treatment for severe detrusor overactivity. Eighteen were followed up for more than 4 years (mean 6.2). Thirteen of the 22 patients had significant symptomatic improvement lasting for more than 4 years post-operatively (59%), 8 of whom had stable bladders. It was concluded that this operation still has a place in the treatment of detrusor overactivity.

Adolescent↗

Sacral nerve stimulation for refractory urge symptoms in elderly patients.

OBJECTIVE: The presence of an overactive detrusor (OD) is becoming more prevalent in the elderly and may severely influence the social life and activities of daily living in the senior, otherwise healthy, person. There is a marked age-dependent increase in OD above the age of 65 years, which is mainly attributed to dysfunction, with loss of voluntary control, of the micturition reflex and decreased perception of bladder fullness. MATERIAL AND METHODS: Herein, we evaluate the outcome of sacral nerve stimulation in five patients aged >65 years derived from a large, multinational, randomized, prospective study. RESULTS: The effect on symptoms was excellent in two subjects. There was a moderate improvement in another subject and a variable but eventually small effect in the remaining two patients. The results appeared to be more favourable in younger patients. CONCLUSION: Our findings suggest that the outcome of sacral nerve stimulation is more unpredictable in the elderly, a fact that should be considered when counselling the patient. However, it should be remembered that, even for the older, active person, urge incontinence may have a severe impact on quality of life and that the majority of patients treated with an implant will benefit from this treatment.

Aged↗

Sacral neuromodulation for chronic pain conditions.

Some of the pelvic pain syndromes seem to have features of neurogenic inflammation and neuropathic pain in common. As opposed to being separate disease entities, they may represent a spectrum of clinical presentations of CRPS I of the pelvis. Sacral nerve root stimulation provides good symptomatic relief of pain and voiding dysfunction. The techniques of retrograde root stimulation may offer superior results with fewer complications and lead migrations when compared with other methods. Perhaps neuromodulation should be used earlier in the treatment paradigm for these disorders, before the potentially injurious procedures of hydrodistention, bladder installations, and cystectomies.

Adult↗