Urodynamics in patients with multiple sclerosis: A consensus statement from a urodynamic experts working group.

AIMS: Urodynamics (UDS) is often indicated for multiple sclerosis (MS) patients either at presentation to specialized medical centers or after failure of conservative management of lower urinary tract dysfunction (LUTD). However, the ideal moment and context to indicate this exam in this group of patients remain controversial. We aimed to establish a consensus panel to address the role of UDS in MS patients. METHODS: A panel representing urology, rehabilitation medicine, and neurology skilled in neuro-urology participated in a consensus-forming project using a Delphi method to reach consensus on the role of UDS in MS patients. RESULTS: In total, five experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥70% of the experts agreed on recommendations. To facilitate a common understanding among all experts, a face-to-face consensus meeting was held in Florence in September 2017 and then with a follow-up teleconference in March 2018. By the end of the Delphi process, formal consensus was achieved for 100% of the items and an algorithm was then developed in a face-to-face meeting in Philadelphia in August 2018. The final expert opinion recommendations were approved by the unanimous consensus of the panel. CONCLUSIONS: UDS represents an important diagnostic tool for MS patients and is particularly useful to evaluate the pattern of LUT dysfunction in high-risk patients. There is a lack of high-evidence level studies to support an optimal urodynamic long-term follow-up protocol.

Screening for urinary incontinence in acute care for elders unit: comparative performance analysis of Katz's ADL and ICIQ-UI-SF.

BACKGROUND: Urinary incontinence (UI) is a frequent, but neglected geriatric syndrome, particularly in vulnerable older patients. Optimizing screening procedures is necessary. OBJECTIVE: To compare the clinometric performances of the "continence" item of the Katz's ADL scale and the ICIQ-UI-sf for the screening of UI in vulnerable aged patients. METHODS: A prospective study was conducted in the acute care for elders (ACE) unit of an academic centre. Two independent nurses screened all patients with spontaneous urination for UI with Katz's ADL item and ICIQ-UI-sf upon the hospital admission. The diagnosis of UI resulted from an interdisciplinary conciliating meeting for urinary functional disorders (TOFU), gathering geriatricians and neuro-urologists and was considered as reference. RESULTS: 294 consecutive patients (mean age 86.2 ± 6.5 years; 76.5% female) admitted to the ACE unit were screened; 169 were incontinent (57.5%) according to TOFU. The Katz's ADL item identified 106 incontinent patients with 20 false positives; 83 incontinent patients were not identified. If the sensitivity and specificity of the ICIQ-UI-sf were 100.0%, they were, respectively, 50.9 and 84.0% for the Katz's ADL item. Positive and negative predictive values were 100.0% for ICIQ-UI-sf; 81.1 and 55.9% for ADL, respectively. CONCLUSION: This study validates the ICIQ-UI-sf as a simple and effective screening tool for UI in vulnerable and complex hospitalized aged patients. It also demonstrates that the "continence" item of the Katz's ADL scale is not sensitive enough for UI screening in this population.

Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder symptoms.

INTRODUCTION: Intravesical botulinum toxin (BoNT-A) is a safe and effective treatment for overactive bladder syndrome. There are many reports on the clinical experience with BoNT-A, especially in patients with neurogenic detrusor overactivity. The US Food and Drug Administration has recently approved its use for idiopathic overactive bladder (iOAB). Various studies have reported positive results for iOAB in the short-term. Yet little is known about the results after repeated BoNT-A injections. In this study, we evaluated the long-term results of botulinum toxin (BoNT-A) in women with iOAB. METHODS: Patients treated with BoNT-A from 2004 until 2009 were evaluated in a non-academic teaching hospital (Zuyderland MC, Heerlen, the Netherlands). All female patients with a follow-up of >5 years with idiopathic bladder dysfunction were included. All patients received 200 U of onabotulinum toxin-A in 20 intradetrusor injections. In some patients, we applied a dose adjustment for repeated injections. Patients were instructed how to use clean intermittent self-catheterization (CISC) before the treatment. We advised patients to commence CISC if post-void residual exceeded 150 ml. RESULTS: A total of 128 women were included. All patients had at least 5-year follow-up after their first injection. The mean follow-up was 97 (60-125) months. The mean age was 67 (46-88) years. Of all patients, 30 % were still on BoNT-A treatment at the last follow-up visit. Of the 70 % that discontinued treatment, 27 % had insufficient effect and 43 % had tolerability issues. Most patients discontinued treatment after the first (79 %) and second (19 %) injections. Only 2 % of patients discontinued treatment after more than two injections during follow-up. CONCLUSION: Intravesical BoNT-A is an effective treatment for women with idiopathic OAB. However, in time, almost two-thirds of patients in our study discontinued therapy. Most patients discontinue treatment after one or two injections and mainly due to tolerability issues.

[Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey]. / Définition et prise en charge de l'échec d'une première injection de toxine botulique Botox ® 200 U pour hyperactivité détrusorienne neurogène: résultats de l'enquête DETOX.

OBJECTIVE: There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. METHODS: A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. RESULTS: Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). CONCLUSION: This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U, repeat injection of Botox(®) 300 U should be the first line treatment.

OnabotulinumtoxinA and multiple sclerosis.

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200 UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200 UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended.

What treatment should we use if drugs fail for OAB; and, what really works after drugs?

AIMS: To determine (using structured brain storm sessions), which treatments should be used if drugs fail for OAB and to determine priority research questions in relation to this issue. METHODS: A frame work for discussion was prepared by the chairman of the session; this included a brief summary of the currently existing evidence. Several experts had been asked to prepare a presentation of their personal treatment algorithm and to identify the [lack of] evidence for such an algorithm. These presentations were summarized by the chairman. Next, this summary was discussed with a large group of experts and opinion leaders and audio-recorded. The proceedings of this process are the basis for this manuscript. RESULTS: The structured sessions resulted in detailed statements about: possible reasons for failure of conservative treatment, the evaluation of outcomes of RCT's, the use of botulinum toxin A in refractory OAB patients, the relative place of neuromodulation or sacral nerve stimulation and botulinum toxin A in the treatment of refractory OAB. CONCLUSIONS: A list of 10 unanswered questions and research topics was compiled. Additionally, 5 top priority research topics were identified.

Neurologic urinary incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic urinary incontinence. METHODS: Through in debt literature review all aspects of neurological urinary incontinence were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment and surgical treatment of neurologic urinary incontinence, levels of evidence and grades of recommendation were made following ICUD criteria. CONCLUSIONS: Though data are available that advice and guide in the management of urinary incontinence in neurologic patients, not many data have a high level of evidence or permit a high grade of recommendation. More and well-structured research is needed.

Neurologic fecal incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic fecal incontinence (FI). METHODS: Through in debt literature review all aspects of neurologic urinary and FI were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment, and surgical treatment of neurologic FI levels of evidence and grades of recommendation were made. CONCLUSIONS: Though data are available that advice and guide in the management of FI in neurologic patients, not many data are with a high level of evidence or high grade of recommendation. More and well-structured research is needed.

Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.

STUDY DESIGN: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. OBJECTIVES: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. METHODS: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. RESULTS: Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. CONCLUSION: Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial.

[Botulinum toxin in nonneurogenic bladder dysfunction]. / Botulinumtoxin bei nichtneurogenen Blasenfunktionsstörungen.

Nonneurogenic overactive bladder with or without detrusor overactivity and/or incontinence is a bothersome symptom for many people. Until a few years ago, it could be treated only with anticholinergic drugs or invasive surgery. Intradetrusor injection with botulinum toxin type A is a minimally invasive alternative therapy option for patients who do not respond to or tolerate anticholinergic treatment. This literature overview summarises the relevant articles on this topic over the last 6 years and provides information on the efficacy, adverse events, currently used dosages, and injection techniques. Overall, a favourable initial efficacy has been observed starting around day 4 after injection and can last up to approximately 31 weeks. Depending on the dose, however, elevated postvoid residual volumes should be anticipated and might require clean intermittent self-catheterisation. The use of botulinum toxin in the urinary bladder is still considered off-label.

International standards to document remaining autonomic function after spinal cord injury.

STUDY DESIGN: Experts opinions consensus. OBJECTIVE: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). BACKGROUND AND RATIONALE: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. METHODS: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. CONCLUSION: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain. METHODS: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and the selected indications. Authors reviewed, abstracted, and classified articles based on the quality of the study (Class I-IV). Conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. RESULTS: The highest quality literature available for the respective indications was as follows: axillary hyperhidrosis (two Class I studies); palmar hyperhidrosis (two Class II studies); drooling (four Class II studies); gustatory sweating (five Class III studies); neurogenic detrusor overactivity (two Class I studies); sphincter detrusor dyssynergia in spinal cord injury (two Class II studies); chronic low back pain (one Class II study); episodic migraine (two Class I and two Class II studies); chronic daily headache (four Class II studies); and chronic tension-type headache (two Class I studies). RECOMMENDATIONS: Botulinum neurotoxin (BoNT) should be offered as a treatment option for the treatment of axillary hyperhidrosis and detrusor overactivity (Level A), should be considered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B), and may be considered for gustatory sweating and low back pain (Level C). BoNT is probably ineffective in episodic migraine and chronic tension-type headache (Level B). There is presently no consistent or strong evidence to permit drawing conclusions on the efficacy of BoNT in chronic daily headache (mainly transformed migraine) (Level U). While clinicians' practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data.

[Pharmacological treatment of neurogenic detrusor hyperactivity: intradetrusor botulinum toxin A injections]. / Traitement pharmacologique de l'hyperactivité détrusorienne neurologique: injections intra-détrusoriennes de toxine botulique A.

Botulinum toxins are among the most powerful of all natural poisons. They are responsible for human botulism and constitute potential chemical weapons, but are nevertheless used as therapeutic agents in an increasing number of indications and medical specialties. Botulinum toxins were used for the first time in urology by intrasphincteric injection by Dykstra in 1988 to treat detrusor-sphincter dyssynergia in spinal cord injury patients. Schurch performed the first intradetrusor injections in 2000 to treat incontinence due to overactive bladder in adult spinal cord injury or multiple sclerosis patients. This review of the literature presents the results and level of proof for the use of botulinum toxin intradetrusor injection to treat neurogenic voiding disorders. Botulinum toxin A intradetrusor injections constitute a safe, conservative, reversible and short-term effective (6-12 months) alternative after failure of anticholinergic therapy for overactive bladder and its clinical consequences in adult spinal cord injury or multiple sclerosis patients (level 1b) and in children with neural tube defects (level 4). The efficacy of the first injection appears to be maintained at subsequent injections (up to 10 cycles) (level 4). Convergent and longer-term data are necessary to document and more clearly define the medium- and long-term efficacy profile of this approach, currently considered to be a major progress in neurourology.

[Quality of life in German-speaking patients with spinal cord injuries and bladder dysfunctions. Validation of the German version of the Qualiveen questionnaire]. / Lebensqualität bei deutschsprachigen Patienten mit Rückenmarkverletzungen und Blasenfunktionsstörungen. Validierung der deutschen Adaption des Qualiveen-Fragebogens.

BACKGROUND: Neurogenic bladder dysfunctions in patients with spinal cord lesions may cause severe limitations in the quality of life (QoL). For assessment of QoL, a validated questionnaire in French is available. The goal of the study was to validate the German version of the questionnaire. METHODS: Translation and intercultural adaptation were achieved in cooperation with an institute for health system research. The resulting German version was filled in by 439 patients in 18 centers in Germany, Austria, and Switzerland. Data were analyzed regarding clinical and sociodemographic characteristics. Quality criteria of the items and scales were tested by a detailed scale analysis. RESULTS: Of the patients 65.8% were paraplegic and 32.8% were tetraplegic. Internal consistency, reliability, and validity of the questionnaire were very good. Differential effects could be displayed in all clinical variables that were tested. CONCLUSIONS: The Qualiveen questionnaire is now available as the first instrument in the German language for the evaluation of the influence of bladder dysfunction on QoL in patients with spinal cord lesions.

Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics.

PURPOSE: In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS: A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS: Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS: Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?

STUDY DESIGN: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland. OBJECTIVES: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved. RESULTS: A 24-h urinalysis detected hypercalciuria--18.7 mmol/day (reference range: 2.5-7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml (reference range: 0.1-0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 (reference range: 2.3-5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day. CONCLUSION: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.

Motor evoked potentials (MEP) and evoked pressure curves (EPC) from the urethral compressive musculature (UCM) by functional magnetic stimulation in healthy volunteers and patients with neurogenic incontinence.

AIMS: The aim of this study is to assess neurogenic lesions of the somatomotor efferent nervous pathway to the urethral compressive musculature (UCM) by means of motor evoked potentials (MEP) and simultaneously recorded evoked pressure curves (EPC). METHODS: Nine healthy subjects and 33 patients (15 spinal cord injury, 14 cauda equina lesion, and 4 multiple sclerosis (MS)) with neurogenic urinary incontinence were prospectively examined by means of urodynamics and electrophysiology. MEP responses from the UCM were evoked after transcranial (tc) and lumbosacral (ls) single pulse magnetic stimulation. A ratio out of tx/ls latencies was calculated to distinguish between central (i.e., spinal) and peripheral lesions. The mechanical UCM pressure responses (=EPC) were recorded simultaneously with electromyographic (EMG) recordings using a microtip pressure transducer catheter with integrated bipolar surface electrodes. RESULTS: In nine healthy subjects the central latency was 19.0 msec, the peripheral latency was 4.25 msec, and the ratio was 4.4. In patients with incomplete spinal cord lesion the central latency was significantly delayed (22.7 msec), whereas the peripheral responses were normal. The ratio (5.5) was increased. Thirteen of these 15 patients suffered from neurogenic incontinence. Patients with a complete spinal lesion showed no UCM reaction after tc stimulation, whereas peripheral responses were normal. Patients with MS showed significantly prolonged central latencies (25.5 msec). The increased ratio of 6.0 indicated a spinal lesion. Ten patients with incomplete cauda equina lesions and urinary incontinence had normal central latencies but prolonged peripheral latencies of 6.7 msec. The ratio of 3.4 indicated a lesion of the sacral caudal roots. In patients with complete cauda injury neither central nor peripheral responses could be evoked. Tc evoked mechanical pressure responses (i.e., contractions) from the UCM could only be recorded in intact or incompletely injured spinal and peripheral motor nervous pathways, whereas they could be evoked after ls stimulation only in cases with partially preserved sacral caudal roots independent of a spinal lesion. CONCLUSIONS: MEP and EPC from the UCM proved to be a well tolerated disgnostic tool in patients with neurogenic incontinence that distinguished central and peripheral lesions of the motor efferent pathways to the UCM.

Lack of ultrastructural detrusor changes following endoscopic injection of botulinum toxin type a in overactive neurogenic bladder.

INTRODUCTION: Endoscopical injections of Botulinum toxin type A into the detrusor muscle are gaining clinical acceptance in the treatment of neurogenic detrusor overactivity. Structural effects of Botulinum toxin type A are only known from studies on striated muscles, where a widespread nerve sprouting occurs temporarily. The aim of this study was to evaluate the ultrastructural effects of Botulinum toxin type A injections on the human detrusor. MATERIAL AND METHODS: 30 detrusor biopsies were obtained from 24 patients with neurogenic detrusor overactivity. Patients were divided into two groups: Group I included 13 biopsies from patients before the first Botulinum toxin type A injection. Group II included 6 biopsies from patients within 3 months after the first injection and 11 biopsies at the time of decreasing efficacy of Botulinum toxin type A. The biopsies were processed by standard procedure for detailed electron microscopic study and evaluated by 2 examiners without prior knowledge of clinical/urodynamic data. RESULTS: No statistically significant detrusor changes have been found concerning muscle cell fascicle structure (p = 0.445), width of intercellular space (p = 0.482) and number/kind of muscle cell junctions (p = 0.443). A median of 70% of intrinsic axon terminals presented with signs of degeneration in group I, a median of 66% in group II (p = 0.840). Out of 309 evaluated axon terminals in both groups, 1 sprouting axon was found in group I, 3 sprouting axons in group II (p = 0.864). Specimen from group I and group II showed only limited collagen deposits within the detrusor. No changes in the ultrastructure of the detrusor have been observed in those biopsies obtained before and after the Botulinum toxin type A injection of the same patient. CONCLUSION: This study verifies our earlier report of severe intrinsic axon degeneration in the detrusor of patients with neurogenic detrusor overactivity. It also shows nearly no structural differences of the detrusor before and after Botulinum toxin type A injections. Contrary to reports of striated muscle, axonal sprouting within the detrusor was very limited after Botulinum toxin type A injections indicating pathophysiologically different reactions to the toxin either between striated muscle and smooth muscle or between different treated diseases.

Increased expression of connexin 43 in the overactive neurogenic detrusor.

PURPOSE: The cellular mechanisms involved in unstable uncontrolled detrusor contractions in the human bladder remain unknown. One hypothesis, based on electron microscopical observations and animal studies, is that gap junctions are present in the human detrusor and are increased in patients with detrusor overactivity. Thus intercellular electrical coupling between adjacent detrusor cells would be increased allowing electrical activity to spead more easily within the detrusor muscle mass and more readily generate significant contractions. The aim of this study was to prove this hypothesis. MATERIAL AND METHODS: Detrusor biopsies have been obtained from videourodynamically evaluated patients with neurogenic detrusor overactivity (NDO) (n = 19) [group I] and from patients with stress urinary incontinence (SUI) with stable, non-obstructed detrusors (n = 5) [group II] serving as controls. Specimens were fixed, paraffin embedded, sectioned, stained with a monoclonal connexin 43 antibody and evaluated by two blinded examiners using a semiquantitative scale. Connexin 43 mRNA levels were evaluated using quantitative RT-PCR with primers for connexin 43 and for 18S rRNA. The results were correlated with the patients' groups. RESULTS: Connexin 43 could be identified in cross sections of every detrusor biopsy. In all biopsies from patients with NDO a widespread presence of connexin 43 staining was observed, whereas only a limited presence of connexin 43 staining was observed in the specimen from patients with SUI. Connexin 43 mRNA levels within the detrusor were 3.7 fold higher in the NDO group than in the SUI group (p = 0.017). CONCLUSIONS: A limited amount of gap junctions seems to be present in every detrusor independently from its urodynamic stability or instability. But there is a significant increase in connexin 43 protein and RNA levels in patients with neurogenic detrusor overactivity underlining their role in intercellular electrical coupling.