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.

Interstitial cystitis/bladder pain syndrome: when part of the posterior fornix syndrome is potentially curable surgically.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as chronic pelvic pain plus a bladder symptom, usually urge. Evidence is offered to show IC/BPS forms part of the posterior fornix syndrome (PFS), which was defined in 1993 as: chronic pelvic pain (CPP), urge, frequency, nocturia, abnormal emptying, post-void residual urine, caused by uterosacral ligament (USL) laxity and cured or improved by USL repair. The IC/BPS definition implies that the urge and pain of IC/BPS is from a single (as yet unknown) pathogenic origin. However, when urge and pain are viewed from the perspective of the PFS, though both have the same lax USL origin, the anatomical pathway from lax USL to symptom manifestation is very different manifestation. For CPP the anatomical pathway is the inability of loose USLs to support pelvic visceral plexuses (VPs); it is hypothesized that inability of weak USLs to mechanically supports VPs, the afferent nerve synapse from end organs may fire off autologous afferent impulses to the brain which interprets them as pain from end organs such as urothelium, vulva, lower abdomen. For urge, the anatomical pathway is very different: lax USLs weaken the directional pelvic muscle forces which stretch the vagina to support the urothelial stretch receptors. The receptors fire off afferent impulses to the cortex at a lower bladder volume, and these are interpreted as "urge to go". Mechanical support of USLs relieves both pain and urge, as does USL repair.

Developing new ways to assess neural control of pelvic organ function in spinal conditions: ICI-RS 2023.

OBJECTIVES: Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms. METHODS: This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction. RESULTS: Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure? CONCLUSIONS: Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back.

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 do X-ray images of the bladder during video urodynamics show us in patients with spinal cord injury?

STUDY DESIGN: Retrospective anonymized cohort study. OBJECTIVES: To study X-ray images of video urodynamics (VUD) in patients with spinal cord injury (SCI). SETTING: Single-center study. METHODS: X-ray images during VUD were categorized. Relation with the American Spinal Injury Association Impairment Scale (AIS), time since and level of SCI, cystometric data, method of bladder management, findings of flexible cystoscopy, and renal ultrasound were evaluated. Changes over time were studied. RESULTS: In 231 consecutive patients, VUD was done at a mean of 8.5 years after SCI. X3-ray bladder appearance was categorized as normal/standard, tonic, or flaccid. In 19 patients, specific findings were seen: diverticula, cystocele, vesicoureteral reflux. X-ray images differed by maximum cystometric capacity, presence of neurogenic detrusor overactivity, and maximum detrusor pressure during detrusor overactivity, but not by bladder compliance. There was no difference in the categories found in different levels and completeness of SCI. In the 23 patients able to void no pathology was seen on urethral images. Renal ultrasound was normal in >99%. In 86 patients, repeated testing after 72 ± 143 weeks showed changed findings in 30%. Cystoscopy showed significantly more local pathologies. CONCLUSION: Complications in the lower urinary tract were seen on imaging only in a limited number of our cohort. As our findings represent a real-life example of the actual yield of VUD in patients with neurogenic bladder due to SCI treated following the international guidelines, further multicentre evaluation is needed to determine when imaging should be used or not.

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.

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.

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.

Sensations Reported During Urodynamic Bladder Filling in Spinal Cord Injury Patients Give Additional Important Information.

PURPOSE: This study investigated the sensations reported during filling cystometry in patients with spinal cord lesions (SCLs) of different levels and completeness. METHODS: In this retrospective cohort study, information was gathered on patients' age and sex, cause of SCL, American Spinal Injury Association Impairment Scale (AIS), and lower urinary tract-related sensations in daily life. Filling cystometry (videourodynamics) was performed following the International Continence Society Good Urodynamic Practice Guidelines. In addition to bladder filling sensations (first sensation of bladder filling, first desire to void, strong desire to void), other sensations, such as detrusor overactivity related sensation and pain, were noted. RESULTS: In total, 170 patients were included (age, 45±17 years; 114 males and 56 females, 92 with complete and 78 with incomplete SCL). The test was done 6±4 years post-SCL. Sensation was reported by 57% of all patients. Half of the patients with complete SCL (46 of 92) had sensation, while 36% of those with incomplete SCL (28 of 78) reported no sensation. Bladder awareness was not predictable by the AIS. The filling sensations reported were equivalent to those given in the terminology of ICS. Pain was seldom present (6%, 10 of 170), and detrusor overactivity contraction was felt by 45 of 78 (58%). Very few patients used sensory information for bladder management at home. CONCLUSION: After SCL, most patients retained the ability to be aware of the lower urinary tract, and were assessable and gradable during urodynamic testing. The filling sensations were not different from those described in healthy individuals, but the number and sequence of the sensations were altered in a minority of patients. Pain and a sensation of unstable contractions gave additional important information. As different sensations relate to different spinal afferent pathways, the sensory evaluation during cystometry provided additional important information on the spinal cord's condition.

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.

Testing sensation of gently squeezing the testes has diagnostic value in spinal cord injury men.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Determine the diagnostic value of testing the sensation of squeezing the testes. SETTING: Research group run by the University of Antwerp. METHODS: During the clinical examination, it was evaluated if male spinal cord injury (SCI) patients felt gentle squeezing of the testes. The outcome was related to the type of SCI, to the sensations of the light touch of the dermatomes of the perineum, of bladder filling, of overactive detrusor (DOA) contractions during urodynamics, and of electrosensation elicited in different parts of the lower urinary tract. The neurological pathways elicited by these tests were compared. RESULTS: Seventy-four patients were included, mean age 46 ± 17 years, a number of weeks post SCI 318 ± 586. Sensation in the testes was present in 72.2%. In patients with AIS A, the sensation was found positive in 41%, while all with AIS B-D felt the sensation. Testes sensation was strongly correlated with the sensation of touch of the perineum and with the filling sensation during cystometry, proving a dorsal column pathway. The sensation of DOA contractions and electrosensation in the bladder, bladder neck/proximal, and distal urethra were not significantly related to the outcome of the testicular examination, showing that anterior and lateral spinothalamic pathways were not involved CONCLUSIONS: Our data show that sensation from gently squeezing the testes informs about the dorsal column from spinal cord level T10-L2 upwards. The test can help refine the neurologic diagnosis after SCI. We advocate to include this easy-to-do test in the neuro-urologic clinical examination.

Combining different evaluations of sensation to assess the afferent innervation of the lower urinary tract after SCI.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To study a combination of three evaluations of sensation in the lower urinary tract (LUT) in patients with spinal cord injury (SCI). SETTING: University Antwerp Belgium, Unicenter study. METHODS: Evaluation of perineal sensation with light digital touch, reporting of filling sensation during a standardised urodynamic investigation and determination of the electrical perception threshold (EPT) were evaluated in patients with SCI. RESULTS: 150 individuals were included: 97 men and 53 women, mean age 46 ± 17 years. Patients had different levels and completeness of SCI, and different techniques for bladder emptying. Seventy-four patients (49%) reported sensation to touch in the perineal area. Sensation of bladder filling was reported in different patterns by 81 patients (54%). EPT was determined in 69 patients of which 50 (72%) reported sensation in different patterns. The outcome of absence/presence of sensation between the three tests differed greatly: with perineal sensation absent 53% had filling sensation (p = 0.040) and 58% positive EPT (p = 0.009). With filling sensation absent 59% had EPT sensation (not significant). Perineal sensation was strongly associated with level and completeness of SCI, while a significant association existed for filling sensations FSF, FDV, SDV and EPT in the distal urethra. CONCLUSIONS: Our study shows that different evaluations of sensation in the LUT of individuals with SCI complement each other. and we therefore propose combined use in the urological evaluation of patients with SCI to allow a more complete picture of the LUT sensations.

Development Signs in Healthy Toddlers in Different Stages of Toilet Training: Can They Help Define Readiness and Probability of Success?

There is much uncertainty about when to start toilet training. Age cannot be a strict stand-alone criterion, as every child has its own pace of development. We observed toilet training (TT) related development signs (DS) in healthy toddlers and determined which can help to define the proper time to start TT and to predict success. The study group consisted of 269 healthy children, in different stages of TT: not started, during, and after completion. Sitting stable, picking up small objects, and spontaneously putting objects in containers were present in all children and had no predictive value. All other DS were significantly more present in those who had started and became more prevalent during completion of TT. Age had a significant association with 13/15 DS. Understanding and following instructions, and having a broader vocabulary were significantly more present when TT had been started. Dry during midday nap reached no significance.

Bladder Pain Syndrome and Interstitial Cystitis Beyond Horizon: Reports from the Global Interstitial Cystitis/Bladder Pain Society (GIBS) Meeting 2019 Mumbai - India.

PURPOSE OF THE MEETING: Bladder pain syndrome/interstitial cystitis is a prevalent but underserved disease. At the Global Interstitial Cystitis/Bladder Pain Syndrome Society (GIBS) meeting, the organization and participants were committed to delivering word-class expertise and collaboration in research and patient care. Under the umbrella of GIBS, leading research scholars from different backgrounds and specialties, as well as clinicians, from across the globe interested in the science and art of practice of Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) were invited to deliberate on various dimensions of this disease. The meeting aimed to have global guidelines to establish firm directions to practicing clinicians and patients alike on the diagnosis and treatment of this disease entity. Chronic Pelvic Pain Syndrome (CPPS) is defined by pain in the pelvic area that can have different etiologies. This can be due to urologic, gynecologic, musculoskeletal, gastrointestinal, neurologic, and autoimmune or rheumatologic diseases. At the GIBS meeting held in Mumbai, India, in August 2019, a multidisciplinary expert panel of international urologists, gynecologists, pain specialists, and dietitians took part in a think tank to discuss the development of evidence-based diagnostic and treatment algorithms for BPS/IC. SUMMARY OF PRESENTED FINDINGS: The diagnosis of BPS/IC is difficult in daily clinical practice. Patients with BPS/IC present with a variety of signs and symptoms and clinical test results. Hence, they might be misdiagnosed or underdiagnosed, and the correct diagnosis might take a long time. A good history and physical examination, along with cystoscopy, is a must for the diagnosis of IC/BPS. For the treatment, besides lifestyle management and dietary advice, oral medication and bladder instillation therapy, botulinum toxin, and sacral neuromodulation were discussed. The innovation in bladder instillation applicators, as well as battery-free neuromodulation through the tibial nerve, was discussed, as well. RECOMMENDATION FOR FUTURE RESEARCH: As BPS/IC is complex, for many patients, several treatments are necessary at the same time. This was presented at GIBS 2019 as the piano model. In this way, a combination of treatments is tailored to an individual patient depending on the symptoms, age, and patients' characteristics. In the art of medicine, especially when dealing with BPS/IC patients, pressing the right key at the right time makes the difference.

Should we be revisiting LUT basic science and clinical measurement of LUT sensation to improve patient care? ICI-RS 2019.

AIMS: This article reviews current knowledge of the underpinning mechanisms of how the bladder senses fullness locally and also revisits clinical measurements of lower urinary tract sensation. The former represents cellular sensing during bladder filling whereas the latter describes the sensations leading to conscious perception of bladder fullness. METHODS: The topic was discussed in a "think tank" session at the 2019 International Consultation on Incontinence-Research Symposium in Bristol, UK; summarized in the present review. RESULTS: Recent advances in the basic science of bladder sensing relating to (a) the bladder wall-urothelial cells, sensory nerves, interstitial cells, and smooth muscle cells and (b) putative chemo/mechanosensors in the urethra-paraneurons or "brush cells" are discussed. Validated clinical measurement of lower urinary tract sensation is reviewed in the context of how this could be better harnessed for patient benefit. We discuss the potential of app/tablet/mobile technology based on triggers and distractors to override aberrant local sensing/higher sensation and how these technologies could be utilized in treatment. CONCLUSIONS: We conclude that a better understanding of bladder sensation is essential to inform clinical management of lower urinary tract symptoms.

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.