Peripheral muscle force balance/imbalance in neurological binary control of bladder function and dysfunction.

Bladder control is not from the bladder itself but from muscles and ligaments outside of it. Bladder control is binary, either closed or open. Control is exerted cortically, directly and via a peripheral pelvic mechanism comprising three reflex pelvic muscles which contract (variously) against pubourethral ligaments (PULs) anteriorly and uterosacral ligaments (USLs) posteriorly. Directed efferent impulses from the cortex close the urethra, open it, and stretch the vagina in opposite directions to prevent urothelial impulses inappropriately activating micturition (urge incontinence). Normally, the opposite muscles are equivalent in force, and balance at the bladder neck. Weak PULs weaken the forward closure force: the posterior forces become relatively more powerful; balance shifts behind bladder neck; the posterior urethral wall is pulled open like a trapdoor, and urine is lost on effort (stress urinary incontinence). Weak USLs weaken the posterior muscle forces; the balance of forces shifts forwards, and the urethra is closed relatively more tightly by slow-twitch forward muscle vector forces (pubococcygei), which stretch each side of the distal vagina forwards to compress the posterior urethral wall; in consequence, the weakened posterior muscle forces cannot easily open the posterior urethral wall; the bladder has to contract against a relatively unopened urethra, perceived as "obstructed micturition". Nor can weakened posterior forces stretch the vagina sufficiently to support the urothelial stretch receptors from below; these may fire off excess afferent impulses to cause urgency. As bladder control is strictly binary, in women with urgency, control swings between open and closed modes. This condition is known as an "unstable bladder", which is defined symptomatically as "overactive bladder", and urodynamically as "detrusor overactivity". In summary, bladder control is binary, either closed or open. How the cortex integrates and computes multiple inputs determines the type of closure, opening or unstable control which is experienced by the patient.

A brief physiology and pathophysiology of the bladder.

The remit of this review is confined to experimental works and publications relevant to the integral theory of female urinary incontinence (IT). Since its first publication in 1990, the IT has challenged the general view that the pathogenesis of overactive bladder (OAB) (urge, frequency, nocturia) is unknown and there is no cure. According to the IT, normal function bladder control is binary, either closed or open. Control is cortical via a peripheral feedback component: oppositely acting reflex striated pelvic muscles contract against suspensory ligaments to close the urethra for continence, open it prior to evacuation, and stretch the vagina like a trampoline to prevent excess impulses from the urothelial stretch receptors which may cause unwanted urgency at low bladder volumes (OAB). The pathogenesis of female urinary incontinence is from outside the bladder, mainly weak ligaments or vagina, due to collagen deficiency. Damage in childbirth (collagen depolymerization) and age (collagen loss) make ligaments vulnerable to damage. With weak ligaments, muscles contracting against them weaken: the muscles cannot close the urethra (manifested as stress incontinence), open it (manifested as emptying problems or retention) or stretch the vagina to prevent the urothelial stretch receptors firing off prematurely (manifested as urge incontinence). Weak pubourethral ligaments can cause stress urinary incontinence (SUI), or SUI plus urge (mixed incontinence). Weak uterosacral ligaments (USLs) can cause urge, frequency, nocturia and emptying difficulties. Treatment consisting of surgical/non-surgical strengthening of ligaments can cure or improve SUI, OAB, and emptying dysfunctions. In summary, bladder control is from outside the bladder, binary, with cortical and peripheral components. A small change in definition, from "overactive" to "overactivated" is consistent with this concept, retains the acronym "OAB", and opens the door to probability of cure and a massive increase in research endeavours.

Defining urge as an uncontrolled micturition explains pathogenesis, informs cure and helps solve the burgeoning OAB crisis.

BACKGROUND: Parallel with the demographic ageing crisis, is a disabling overactive bladder (OAB) crisis (urgency/frequency/nocturia), 30% prevalence in older women, pathogenesis stated as unknown and, according to some learned societies, incurable. HYPOTHESIS/AIMS: To review International Continence Society and Integral System paradigms to test our thesis that OAB per se is not a pathological condition, rather, a prematurely activated uncontrolled micturition; pathogenesis being anatomical damage in a nonlinear feedback control system comprising cortical and peripheral (muscle/ligament) components. METHODS: We examined studies from basic science, anatomy, urodynamics, ultrasonic and video xrays, ligament repairs, from which we created a nonlinear binary model of bladder function. We applied a Chaos Theory feedback equation, Xnext = Xc(1 - X) to test our hypothesis against existing concepts and hypotheses for OAB pathogenesis. RESULTS: The bladder has ONLY two modes, EITHER closed OR open (micturition). Closure is reflexly controlled cortically and peripherally: muscles contracting against ligaments stretch the vagina to suppress afferent signals to micturate from urothelial stretch receptors. "OAB" can be caused by anatomical damage anywhere in the model, by childbirth or age-weakened ligaments, which can be repaired to cure all three OAB symptoms. Urodynamic "DO" graphs are interpreted anatomically and by the feedback equation. CONCLUSION: OAB is in crisis. Our thesis of OAB as an uncontrolled micturition from anatomical defects in the bladder control system provides fresh directions for further development of new treatments, nonsurgical and surgical, to help break the crisis and bring hope and cure to 600 million women sufferers.

What is the clinical meaning of a negative bulbocavernosus reflex in spinal cord injury patients?

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: To highlight some issues about the clinical meaning of a negative bulbocavernosus reflex (BCR) in spinal cord injury (SCI) patients. SETTINGS: Research group University Antwerp Belgium. METHODS: The study included 170 patients in whom the BCR was examined at a mean of 7 years post SCI. Changes over time were explored in a subset of patients. RESULTS: BCR was negative in 45%. There was no influence of age and gender, nor could a relation be found with the American Spinal Injury Association Impairment Scale score. The anal sphincter reflex (ASR) was positive in 13% of patients with negative BCR. With a mean interval of 45 weeks, BCR changed in 32% of a subset of 44 patients (14 became positive, 3 negative), while the neurological condition did not change and no treatments had been given that could influence the outcome. The data show that a negative BCR may not only be due to a disrupted reflex nervous pathway (which in some patients is different from that of ASR), but may also be caused by a difficulty to provoke the reflex. CONCLUSION: A negative BCR test indicates interruption of the reflex neurologic pathways, but can also depend on the ease to elicit the reflex. By also doing ASR, this dilemma can be partly solved.

Overactive bladder (OAB): a failed concept needing revision to accommodate an external anatomical control system.

THESIS AND AIMS: In 45 years, the definitions and practice of the urodynamically based overactive bladder (OAB)/detrusor overactivity (DO) system have failed to adequately address pathogenesis and cure of urinary urge incontinence, frequency and nocturia. METHODS: We analysed the OAB syndrome with reference to the Integral Theory paradigm's (ITS) binary feedback system, where OAB in the female is viewed as a prematurely activated, but otherwise normal micturition caused mainly, but not entirely, by ligament damage/laxity. The ITS Clinical Assessment Pathway which details the relationships between structural damage (prolapse), ligaments and dysfunction (symptoms) is introduced. RESULTS: The ITS was able to "better explain" OAB pathophysiology in anatomical terms with reference to the binary model. The phasic patterns diagnostic of "detrusor overactivity" are explained as a struggle for control by the closure and micturition reflexes. The exponentially determined relationship between urethral diameter and flow explains why obstructive patterns occur, why they do not and why urine may leak with no recorded pressure. Mechanically supporting ligaments ("simulated operations") during urodynamic testing can improve low urethral pressure, negative pressure during coughing with SUI and diminish urge sensation or even DO patterns, transforming urodynamics from non-predictive test to accurate predictor of continence surgery results. High cure rates for OAB by daycare repair of damaged ligaments is a definitive test of the binary system's validity. CONCLUSION: Conceptual progression of OAB to the Integral Theory paradigms's prematurely activated micturition validates OAB component symptoms as a syndrome, explains pathogenesis, and unlocks a new way of understanding, diagnosing, treating and researching OAB.

An anatomical pathogenesis of lower urinary tract definitions from the 2002 ICS report symptoms, conditions, syndromes, urodynamics.

AIM: To present an anatomical pathogenesis parallel with the 2002 International Continence Society Lower Urinary Tract (LUTS) definitions standardization Report 2002. METHODS: Each LUTS section is discussed using the same numbers as the Report. RESULTS: Normal function Bladder control is binary, with two reflexes alternating, either closure (dominant) or open (micturition), with the same cortical and peripheral components: three directional muscle forces contracting against pubourethral (PUL) and uterosacral (USL) ligaments for closure, two against uterosacral ligaments for micturition. Dysfunction OAB symptoms reflect a prematurely activated micturition; PUL/USL weakness prevents muscle forces from controlling afferent urothelial emptying signals. Stress urinary incontinence is a consequence of weak PULs allowing posterior muscle forces to open the urethra during effort. Lax USLs weaken contractile force of the posterior urethral opening vectors, so detrusor has to contract against an unopened urethra. This is experienced as "obstructive micturition." CONCLUSIONS: Anatomical analysis indicates the ICS definitions are fundamentally sound, except for "OAB" which implies detrusor causation. Minor changes, OAB to "overactivated" bladder allow causation outside of bladder. This construct supports OAB and its component symptoms as a syndrome, as intuited by the Committee, (albeit as a prematurely activated micturition), retains the acronym, explains OAB cure by ligament repair, and incontinence pathogenesis from two post-2002 syndromes which need an addition to the definitions, Posterior Fornix Syndrome (of which OAB is a component) and Tethered Vagina Syndrome, which is the basis for skin-grafting cure of the 30%-50% of women who continue leaking urine massively after successful obstetric fistula closure.

Pelvic-floor function, dysfunction, and treatment.

The pelvic floor functions as a holistic entity. The organs, bladder, bowel, smooth and striated muscles, nerves, ligaments and other connective tissues are directed cortically and reflexly from various levels of the nervous system. Such holistic integration is essential for the system's multiple functions, for example, pelvic girdle stability, continence, voiding/defecation, and sexuality. Pelvic floor dysfunction (PFD) is related to a variety of pelvic pain syndromes and organ problems of continence and evacuation. Prior to treatment, it is necessary to understand which part(s) of the system may be causing the dysfunction (s) of Chronic Pelvic Pain Syndrome (CPPS), pelvic girdle pain, sexual problems, Lower Urinary Tract Symptoms (LUTS), dysfunctional voiding, constipation, prolapse and incontinence. The interpretation of pelvic floor biomechanics is complex and involves multiple theories. Non-surgical treatment of PFD requires correct diagnosis and correctly supervised pelvic floor training. The aims of this review are to analyze pelvic function and dysfunction. Because it is a holistic and entirely anatomically based system, we have accorded significant weight to the Integral Theory's explanations of function and dysfunction.

The innervation of the bladder, the pelvic floor, and emotion: A review.

The innervation of the pelvic region is complex and includes extensive neurologic pathways. The higher centres' organisation determining the pelvic floor and organs' function remains a challenge understanding the physiological and pain mechanisms. Psychological and emotional factors have a profound influence on the pelvic floor and organ dysfunction such as LUTS. LUTS are associated with stress, depression, and anxiety. Neuroception is a subconscious neuronal system for detecting threats and safety and might explain the permanent disturbance of higher brain centres maintaining functional urological and gastrointestinal disorders and sphincter dysfunction.

Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report.

Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype.Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes.Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other.Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.

Pain areas and mechanosensitivity in patients with chronic pelvic pain syndrome: a controlled clinical investigation.

OBJECTIVE: A thorough clinical assessment including physical examination is crucial in a diagnostic work-up, including in patients with chronic pelvic pain syndrome (CPPS). This study investigated the prevalence of pain areas and the mechanosensitivity of peripheral nerves in patients with CPPS and compared the findings with a healthy control group. MATERIALS AND METHODS: Healthy volunteers and patients diagnosed with CPPS were assessed with physical examinations and neurodynamic testing. RESULTS: The CPPS group (n = 26) and the control group (n = 28) showed no statistical differences between males and females for age and body mass index (Mann-Whitney U test). The patients in the CPPS group were significantly older and had a significantly higher weight compared to controls. Healthy volunteers did not show any pain area or mechanosensitivity of the examined peripheral nerves of the lumbosacral plexus. Patients with CPPS showed a variety of pain from different musculoskeletal origins. Neurodynamic testing demonstrated significant mechanosensitivity in at least one nerve of the lumbosacral plexus in 88% of the patients with CPPS, suggesting minor nerve injuries. Pudendal nerve mechanosensitivity was found in 85% of patients, while 42% had multiple nerves involved. Unilateral or bilateral pudendal channel palpatory pain was present in 62% of the CPPS group and not in controls. CONCLUSIONS: This study shows musculoskeletal pain and a high prevalence of minor nerve injuries in CPPS patients, indicating the presence of abnormal impulse generation sites that can help in understanding the clinical picture in CPPS patients and guiding their treatment.

Primo Vascular System: A Unique Biological System Shifting a Medical Paradigm.

The primo vascular system has a specific anatomical and immunohistochemical signature that sets it apart from the arteriovenous and lymphatic systems. With immune and endocrine functions, the primo vascular system has been found to play a large role in biological processes, including tissue regeneration, inflammation, and cancer metastases. Although scientifically confirmed in 2002, the original discovery was made in the early 1960s by Bong-Han Kim, a North Korean scientist. It would take nearly 40 years after that discovery for scientists to revisit Kim's research to confirm the early findings. The presence of primo vessels in and around blood and lymph vessels, nerves, viscera, and fascia, as well as in the brain and spinal cord, reveals a common link that could potentially open novel possibilities of integration with cranial, lymphatic, visceral, and fascial approaches in manual medicine.

Chronic pelvic pain syndrome: role of a thorough clinical assessment.

Chronic pelvic pain syndrome (CPPS) presents with a variety of symptoms affecting multiple systems. There is no universal treatment that can be given to all patients with CPPS. The results of treatment depend greatly on an accurate diagnosis. A thorough clinical assessment, including a "four-step plan", should include paying special attention to the musculoskeletal system. This assessment is not difficult to perform and provides valuable information on possible muscular problems and neuropathy.

Prevalence of lower urinary tract symptoms and level of quality of life in men and women with chronic pelvic pain.

OBJECTIVES: The aim of this study was to evaluate the prevalence of lower urinary tract symptoms and quality of life in patients with chronic pelvic pain syndrome (CPPS). MATERIALS AND METHODS: The McGill Pain Questionnaire, Dutch Leiden/Leuven Version (MPQ-DLV), Pain Disability Index (PDI), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Interstitial Cystitis Symptom Index (ICSI) and Pelvic Pain and Urinary/Frequency Symptom Scale (PUF) were used, based on their specific properties, to assess the symptoms and impact on the quality of life. Total scores and domains were compared for gender. RESULTS: The studied group (N = 35; 18 male, 17 female) showed a good distribution in gender for age [Mann-Whitney U test (MW-U) p = 0.4] and body mass index (MW-U p = 0.2). The MPQ-DLV showed significantly higher scores for pain in women for Pain Rating Index - Affective (MW-U p = 0.030) and Total (MW-U p = 0.031), and Visual Analogue Scale for Pain - Most (MW-U p = 0.005). Women were less sexually active (PUF-SA) (chi-squared test p = 0.021) and had a significantly higher disability (PDI-T) (MW-U p = 0.005) and MPQ - Quality of Life (MW-U p = 0.003). The urinary symptoms showed similar results for gender (chi-squared test p > 0.05). CONCLUSIONS: A wide variety of symptoms and a negative impact on quality of life were shown. No differences in lower urinary tract symptoms were found between genders. Women were less sexually active than men. Chronic pelvic pain had a significantly higher negative impact on the level of quality of life in women than in men.

Variability of pudendal and median nerve sensory perception thresholds in healthy persons.

BACKGROUND: Normative current perception thresholds (CPTs) are used for the evaluation of sensory function in a variety of diseases. AIMS: To evaluate the reproducibility of CPT measurements with sinusoidal current in healthy volunteers. METHODS: Neuroselective CPT evaluations of the median and pudendal nerve in healthy volunteers were repeated with 1 week interval (T1 and T2). RESULTS: In the study group (N = 41) no difference between genders for age (MW-U: P = 0.91) and BMI (t-test: P = 0.18) were found. No significant difference between T1 and T2 was found (Paired t-test: all P-values > 0.05), although the intraclass correlation for each person was low. The variability of measures for the pudendal nerve was: ICC 2 kHz: 0.41; 250 Hz: 0.30; 5 Hz: 0.38, and for the median nerve respectively: 0.58; 0.46; 0.40. Normal CPTs were shown for the pudendal nerve: 2 kHz: 51%; 250 Hz: 76%; 5 Hz: 71%, and median nerve respectively: 78%; 98%; 80%. The pudendal nerve showed more deviating values compared to the median nerve. CONCLUSION: Both nerves showed deviating values. CPT values with sinusoidal current assessed with 1 week interval, showed a weak intraclass correlation. This finding limits the use of CPT values with this current for longitudinal studies.

Pudendal and median nerve sensory perception threshold: a comparison between normative studies.

BACKGROUND: For the evaluation of sensory innervation, normative data are necessary as a comparison. AIMS: To compare our current perception thresholds (CPTs) with normative data from other research. METHODS: Healthy volunteers were assessed for 2000, 250, and 5 Hz CPTs of the median and pudendal nerve and data were compared with other studies. RESULTS: Normative data in the studied group n = 41 (male: 21; female: 20) for the median nerve, 2 kHz, 250 Hz, and 5 Hz were respectively: 241.85 ± 67.72 (140-444); 106.27 ± 39.12 (45-229); 82.05 ± 43.40 (13-271). Pudendal nerve CPTs 250 Hz were: 126.44 ± 69.46 (6-333). For men 2 kHz: 349.95 ± 125.76 (100-588); 5 Hz: 132.67 ± 51.81 (59-249) and women 2 kHz:226.20 ± 119.65 (64-528); 5 Hz: 92.45 ± 44.66 (35-215). For the median nerve no statistical differences for gender were shown. For the pudendal nerve, only 250 Hz showed no difference for gender (t-test: 0.516). Comparison of our data with CPTs of other normative data showed no agreement for the pudendal nerve. For the median nerve only 2 kHz showed agreement in three studies and for 5 Hz with one study. CONCLUSION: Comparing normative data of multiple studies shows a variety of results and poor agreement. Therefore, referring to normative data of other studies should be handled with caution.

Reassessing cerebrospinal fluid (CSF) hydrodynamics: a literature review presenting a novel hypothesis for CSF physiology.

The traditional model of cerebrospinal fluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments.

Comparison of questionnaires used for the evaluation of patients with chronic pelvic pain.

AIMS: Comparison of questionnaires for the evaluation of symptoms and QoL in patients with CPPS. METHODS: The MPQ-DLV, PDI, NIH-CPSI, ICSI, and PUF, were compared for: pain, bladder complaints, and for QoL. RESULTS: The studied group N = 26 (male: 16; female: 10) showed a good distribution in gender for the age (MW-U: P = 0.6) and BMI (MW-U: P = 0.5). The intraclass correlation (ICC) for pain intensity of MPQ-NWC and MPQ-PRIT was 0.55. The ICC's, for other different pain intensity scores were mostly <0.25 (global = 0.23). For bladder complaints a positive global score (ICC = 0.64) was shown, with the score for NIH-CPSI and ICSI > 0.77. The ICC for NIH-CPSI and PUF-SS was the lowest (=0.48). The QoL showed a global bad correlation (ICC ≤ 0.27) with MPQ-DLV-QoL/PDI, PDI/ICPI, PDI/PUF-BS and ICPI/PUF-BS scoring >0.5. CONCLUSION: When the most used questionnaires for QoL assessment in patients with CPPS are compared, very different results can be found. This indicates that results from one questionnaire cannot be used for overall conclusions concerning pain intensity and QoL. For bladder symptoms the results seem to correspond better. To develop one generally accepted questionnaire would facilitate the interpretation and comparison of data in this condition.