Regional Clustering of Giggle Incontinence in Toyserkan, Iran: A Case Series of 20 Patients

Regional Clustering of Giggle Incontinence in Toyserkan, Iran: A Case Series of 20 Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Regional Clustering of Giggle Incontinence in Toyserkan, Iran: A Case Series of 20 Patients Farshad Banouei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7842510/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose Giggle incontinence (enuresis risoria) is a rare condition characterized by complete involuntary bladder emptying triggered by laughter. Limited epidemiological data exist regarding its prevalence and geographic distribution.To report an unexpectedly high incidence of giggle incontinence cases in Toyserkan, Iran, and describe the clinical characteristics, treatment responses, and potential familial clustering in this regional population. Methods A retrospective case series of 20 consecutive patients diagnosed with giggle incontinence between 2023 and 2025 at Toyserkan Hospital. Clinical characteristics, family history, treatment modalities, and outcomes were systematically documented and analyzed. Results Twenty patients (age range: 4–19 years, mean age: 7.65 ± 2.38 years) were diagnosed with giggle incontinence in a city with a population of 100,000. The mean symptom duration before presentation was 1.5 years (range: 1–2 years). All patients presented with severe involuntary complete bladder emptying triggered exclusively by laughter. Diagnosis was confirmed through comprehensive history taking, physical examination, laboratory tests, and imaging studies. Familial clustering was observed in 15% of cases, including one family with three affected siblings. All patients initially received behavioral modifications, which showed poor adherence and minimal efficacy. Subsequently, all 20 patients were treated with tolterodine (1–2 mg every 12 hours). Treatment outcomes showed complete resolution in 3 patients (15%), partial improvement in 6 patients (30%), and no response in 11 patients (55%) after minimum 3-month trial. Long-term follow-up (minimum 2 years) revealed sustained response in most initial responders, with some spontaneous improvement in non-responders over time. The prevalence rate of 20 cases per 100,000 population over two years appears substantially higher than previously reported international rates. Conclusions This case series reveals a potential regional cluster of giggle incontinence in Toyserkan, Iran, with notable familial aggregation and treatment resistance. The findings suggest possible genetic predisposition or environmental factors specific to this geographic region, warranting further epidemiological investigation and genetic studies. Giggle incontinence Enuresis risoria Regional clustering Familial aggregation Pediatric urology Introduction Giggle incontinence, also known as enuresis risoria, is a rare and poorly understood condition characterized by sudden, complete, and involuntary bladder emptying triggered exclusively by laughter. Unlike stress urinary incontinence or other forms of bladder dysfunction, giggle incontinence involves total bladder evacuation during episodes of intense laughter, often leaving patients socially embarrassed and psychologically distressed ( 1 , 2 ). First described systematically by Glahn in 1979 ( 4 ), giggle incontinence predominantly affects children and adolescents, with most cases resolving spontaneously by late adolescence. The exact pathophysiology remains elusive, though proposed mechanisms include transient detrusor-sphincter dyssynergia, neurological factors affecting bladder control during emotional states, and potential genetic predisposition ( 2 , 4 ). Epidemiological data on giggle incontinence are scarce, with most knowledge derived from isolated case reports and small case series, making prevalence estimates difficult ( 1 , 3 ). The condition can significantly impact patients' quality of life, leading to social withdrawal, school absenteeism, and psychological distress ( 2 , 5 ). Treatment approaches have been largely empirical, with variable success rates reported for anticholinergic medications ( 3 , 6 ), methylphenidate ( 3 ), and behavioral interventions ( 7 , 8 ). Between 2023 and 2025, we observed an unexpectedly high number of giggle incontinence cases in our urology practice in Toyserkan, a city in western Iran with a population of approximately 100,000. The concentration of cases, along with observed familial clustering, prompted us to systematically document and analyze this cohort. This case series aims to describe the clinical characteristics, treatment outcomes, and potential regional factors contributing to this apparent cluster of giggle incontinence cases. Materials and Methods Study Design and Setting This retrospective case series included all consecutive patients diagnosed with giggle incontinence at the Department of Urology, Toyserkan Hospital, Toyserkan, Iran, between January 2023 and August 2025. Toyserkan is a city in Hamedan Province, western Iran, with a population of approximately 100,000. Patient Selection Inclusion Criteria: Complete involuntary bladder emptying triggered exclusively by laughter Age < 20 years at presentation Absence of anatomical urinary tract abnormalities No evidence of neurological disease Complete medical records available Exclusion Criteria: Stress urinary incontinence or other forms of incontinence Daytime urinary frequency without laughter trigger Neurogenic bladder dysfunction Anatomical abnormalities of the urinary tract Data Collection Medical records were systematically reviewed for the following variables: Demographic data (age, gender) Age at symptom onset Symptom duration before presentation Episode frequency and severity Family history of giggle incontinence or urinary disorders Physical examination findings Diagnostic test results (urinalysis, ultrasonography, urodynamic studies when performed) Treatment modalities employed Treatment outcomes and follow-up duration Diagnostic Criteria Giggle incontinence was diagnosed based on: 1. Detailed history taking focusing on the temporal relationship between laughter and complete bladder emptying 2. Normal voiding pattern at all other times 3. Complete physical examination including neurological assessment 4. Laboratory investigations: Complete urinalysis and urine culture to exclude infection Basic metabolic panel 5. Imaging studies: Renal and bladder ultrasonography to exclude anatomical abnormalities Urodynamic studies when clinically indicated 6. Exclusion of other causes of urinary incontinence including stress incontinence, urge incontinence, and neurogenic bladder Treatment Protocol Treatment Protocol All patients were initially managed with comprehensive behavioral modifications including: Timed voiding protocols with scheduled bladder emptying before situations likely to provoke laughter Pelvic floor muscle training and exercises Fluid management strategies with avoidance of bladder irritants Counseling regarding social situations and coping mechanisms Pharmacological interventions were implemented when behavioral modifications proved insufficient: Anticholinergic medication : Tolterodine extended-release formulation Dosage: 1–2 mg every 12 hours (twice daily) Treatment duration: Minimum 3 months to assess efficacy All 20 patients received tolterodine as the primary anticholinergic agent All patients were followed for a minimum of 2 years to assess long-term outcomes and spontaneous resolution patterns. Outcome Assessment Treatment outcomes were classified as: Complete resolution : No incontinence episodes for ≥ 3 months Partial improvement : ≥50% reduction in episode frequency No response : <50% reduction in episodes or no change Statistical Analysis Descriptive statistics were used to summarize patient characteristics and outcomes. Continuous variables are presented as mean ± standard deviation or median with range. Categorical variables are presented as frequencies and percentages. Ethical Considerations This study was conducted in accordance with the Declaration of Helsinki. As a retrospective review of medical records with anonymized data, formal ethics committee approval was waived according to institutional guidelines. Patient confidentiality was strictly maintained. Results Patient Demographics Twenty patients were diagnosed with giggle incontinence during the study period. The cohort included patients aged 4 to 19 years (mean age: 7.65 ± 2.38 years; median: 7 years). The gender distribution showed a female predominance with 13 girls (65%) and 7 boys (35%). The age distribution showed clustering in the 6–9 year age group (70% of cases). The mean symptom duration before presentation was 1.5 years (range: 1–2 years). All patients reported severe symptoms with complete bladder emptying during laughter episodes, with variable frequency ranging from several times per week to daily occurrences. Clinical Characteristics All 20 patients presented with the pathognomonic feature of complete involuntary bladder emptying triggered exclusively by laughter. Between episodes, voiding patterns were entirely normal with no daytime frequency, nocturia, or urgency. Physical examinations were unremarkable in all cases. Urinalysis showed no abnormalities, and renal and bladder ultrasonography revealed normal anatomy in all patients. Familial Clustering A notable finding was the observation of familial aggregation in 3 patients (15% of the cohort). One family presented with three affected siblings (ages [to be specified]), representing a striking familial clustering pattern. This familial pattern suggests a potential genetic component to the condition in this population. Treatment Outcomes All patients initially underwent a trial of comprehensive behavioral modifications for a minimum of 3 months. Behavioral interventions, including timed voiding protocols, pelvic floor muscle training, and fluid management strategies, were poorly tolerated and demonstrated minimal clinical efficacy in reducing the frequency or severity of incontinence episodes. Patient adherence to behavioral protocols was suboptimal, likely due to the unpredictable nature of laughter-triggered episodes and the difficulty of implementing preventive strategies in social situations. Subsequently, all 20 patients (100%) were treated with tolterodine extended-release formulation (1–2 mg every 12 hours): Treatment outcomes after a minimum 3-month trial of tolterodine therapy: Complete resolution : 3 patients (15%) - no incontinence episodes for ≥ 3 months Partial improvement : 6 patients (30%) - ≥50% reduction in episode frequency No response : 11 patients (55%) - <50% reduction or no change in symptoms The majority of patients (55%) showed no significant improvement with tolterodine therapy, highlighting the treatment-resistant nature of giggle incontinence in this cohort. Among responders (n = 9, 45%), improvement was typically observed within 4–6 weeks of initiating therapy, though the degree of response varied considerably. Long-term follow-up (minimum 2 years, range: 2-2.5 years) revealed that patients with initial complete or partial response generally maintained their improvement with continued medication. However, some non-responders showed spontaneous improvement over time without pharmacological intervention, consistent with the natural history of potential spontaneous resolution during adolescence. No alternative pharmacological interventions (such as methylphenidate or desmopressin) were systematically employed in this cohort. Regional Prevalence With 20 cases identified over a 2-year period in a population of 100,000, the observed prevalence in Toyserkan appears substantially elevated compared to rates reported in international literature. This concentration of cases within a geographically defined population suggests potential regional clustering. Table 1 . Table 1 Patients data Patient No. Age (years) Gender Symptom Duration (years) Familial Cases Treatment Outcome 1 4 Female 1–2 Yes (Sibling 1/3) Behavioral + Tolterodine 1-2mg q12h No response 2 4 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 3 5 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 4 6 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 5 6 Male 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 6 7 Female 1–2 Yes (Sibling 2/3) Behavioral + Tolterodine 1-2mg q12h Complete resolution 7 7 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 8 7 Male 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 9 7 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 10 7 Male 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 11 7 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Complete resolution 12 8 Male 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 13 8 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 14 9 Male 1–2 Yes (Sibling 3/3) Behavioral + Tolterodine 1-2mg q12h No response 15 9 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 16 9 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 17 9 Male 1–2 No Behavioral + Tolterodine 1-2mg q12h Partial improvement 18 10 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h No response 19 10 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h Complete resolution 20 19 Female 1–2 No Behavioral + Tolterodine 1-2mg q12h No response Discussion This case series represents one of the largest single-center cohorts of giggle incontinence reported in the literature and reveals several clinically significant findings. The concentration of 20 cases in a population of 100,000 over two years suggests a prevalence substantially higher than previously reported rates, raising important questions about regional, genetic, or environmental factors that may predispose certain populations to this condition. Regional Clustering and Potential Mechanisms The apparent regional clustering observed in Toyserkan may be attributed to several factors: Genetic Predisposition The observation of familial clustering in 15% of cases, including one family with three affected siblings, strongly suggests a genetic component. Toyserkan's relative geographic isolation may have resulted in a founder effect or increased prevalence of specific genetic variants predisposing to giggle incontinence. This hypothesis is supported by the known consanguinity rates in Iranian populations and the possibility of recessive inheritance patterns becoming more apparent in genetically homogeneous communities. Environmental Factors Local environmental conditions, dietary patterns, or cultural practices specific to the region may contribute to the observed clustering. Further investigation into potential environmental triggers or protective factors is warranted. Diagnostic Awareness As the only specialized urology center in the region, increased awareness and systematic documentation in our practice may have improved case identification. However, the absolute number of cases and familial clustering patterns suggest this is unlikely to fully explain the phenomenon. Clinical Characteristics and Age Distribution The concentration of cases in the 6–9 year age range (70% of patients) aligns with previous literature suggesting peak incidence during early to middle childhood ( 1 , 2 ). However, the presence of one 19-year-old patient demonstrates that the condition can persist into late adolescence, contrary to the assumption of universal spontaneous resolution ( 4 ). The universal presentation of complete bladder emptying during laughter episodes, with otherwise normal voiding patterns, confirms the distinct clinical phenotype of giggle incontinence and differentiates it from other forms of pediatric incontinence ( 8 ). Treatment Resistance and Clinical Implications The limited efficacy of tolterodine therapy in our cohort (complete resolution in only 15%, no response in 55%) is striking and may suggest that giggle incontinence in this population represents a distinct pathophysiological subtype. This treatment resistance pattern differs from some reports in the literature suggesting better responses to anticholinergics ( 6 ), though variable treatment outcomes have been consistently noted across studies ( 3 ). The pathophysiology of giggle incontinence remains poorly understood. Proposed mechanisms include: Neurological dysregulation : Emotional responses during laughter may trigger abnormal neural signaling affecting bladder control ( 2 , 4 ) Cataplexy-like phenomenon : Some authors have suggested similarities to narcolepsy-cataplexy, given the emotional trigger and complete loss of control ( 4 ) Detrusor-sphincter dyssynergia : Transient incoordination between detrusor contraction and sphincter relaxation during laughter ( 2 ) Genetic factors : Our familial clustering data support inherited susceptibility The treatment resistance observed in our cohort may indicate that the underlying pathophysiology in this regional cluster involves mechanisms less responsive to anticholinergic blockade, potentially supporting a more neurologically-mediated process. The poor response to behavioral interventions further suggests that simple bladder management strategies are insufficient for this condition, which may require more targeted neurological or pharmacological approaches. Familial Aggregation and Genetic Implications The identification of familial clustering in 15% of cases, particularly the family with three affected siblings, provides compelling evidence for genetic predisposition. To our knowledge, such clear familial aggregation has been infrequently reported in the giggle incontinence literature. This finding suggests that genetic studies in this population may be particularly informative for identifying susceptibility genes. Potential genetic mechanisms could include: Autosomal dominant inheritance with variable penetrance Autosomal recessive inheritance (more likely given consanguinity patterns) Polygenic inheritance with environmental modifiers Epigenetic factors influenced by regional environmental conditions Comparison with International Literature Published prevalence data for giggle incontinence are limited, with most estimates derived from small studies suggesting rates well below what we observed ( 1 , 3 ). Our finding of 20 cases per 100,000 population over two years in the pediatric and adolescent age range appears substantially elevated, supporting the hypothesis of true regional clustering rather than ascertainment bias alone. Study Limitations Several limitations must be acknowledged: Retrospective design : Data were collected from medical records, potentially limiting the completeness and standardization of clinical information. Single-center study : While this allowed for consistent diagnostic criteria and management protocols, referral patterns may have influenced case identification. Limited follow-up : Long-term outcomes beyond the immediate treatment period were not consistently available for all patients. Lack of control group : Without systematic screening of the general population, true prevalence estimates remain uncertain. Missing genetic analysis : Formal genetic testing was not performed, limiting our ability to identify specific genetic factors. Incomplete treatment data : Detailed medication dosing, duration, and systematic assessment of all treatment modalities were not uniformly documented. Clinical and Research Implications This case series has several important implications: Increased awareness : Clinicians in other geographically distinct or genetically homogeneous populations should systematically document giggle incontinence cases to identify similar clusters. Genetic investigation : The familial clustering observed warrants formal genetic studies, including whole-exome sequencing of affected families to identify susceptibility genes. Alternative treatment strategies : Given the treatment resistance to anticholinergics, investigation of alternative approaches including methylphenidate ( 3 ), biofeedback ( 7 ), or neuromodulation may be warranted. Epidemiological studies : Systematic population-based screening in the region could provide accurate prevalence estimates and identify additional cases. International collaboration : Establishing registries and collaborative research networks may help identify genetic and environmental risk factors through multi-center studies. Conclusion This case series documents an apparent regional clustering of giggle incontinence in Toyserkan, Iran, with 20 cases identified over two years in a population of 100,000. The notable familial aggregation, treatment resistance to conventional anticholinergic therapy, and geographic concentration suggest potential genetic predisposition or environmental factors specific to this region. These findings highlight the need for systematic epidemiological investigation, genetic studies, and development of alternative treatment strategies for this understudied and often treatment-resistant condition. We encourage international colleagues to systematically document similar cases to advance understanding of giggle incontinence epidemiology and pathophysiology. Declarations Ethics approval and consent to participate: This study was approved by the Ethics Committee of Hamadan University of Medical Sciences (approval number: IR.UMSHA.REC.1400.284) Written informed consent to participate was obtained from the parents or legal guardians of all minor participants, and assent was obtained from participants capable of providing it, in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. This manuscript does not contain any individual person's identifying data, images, or clinical details that would compromise anonymity. All patient data have been anonymized and presented in aggregate form. Competing interests: The authors declare that they have no competing interests. Funding: All sources of funding for the research paid by Farshad Banouei. Author Contribution FB analyzed and interpreted the patient all data, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Glahn BE. Giggle incontinence (enuresis risoria). A study and an aetiological hypothesis. Br J Urol. 1979;51(5):363–6. Giddens JL, Bauer SB, Hallett M, Khoshbin S, Kelly MD, Darbey MM. The giggle incontinence syndrome: a scoping review. Pediatr Res. 2024;95(4):1021–8. Chung JM, Lee SD, Kang DI, Kwon DD, Kim KS, Kim SY, et al. An epidemiologic study of voiding dysfunction in children and adolescents: a population-based study. Neurourol Urodyn. 2010;29(8):1435–40. Weiss JP, Heesakkers JP, van Kerrebroeck PE, Klein BM, Nitti VW. Successful treatment of giggle incontinence with methylphenidate. J Urol. 1996;156(2 Pt 2):656–8. Berry AK. Helping children with nocturnal enuresis: the wait-and-see approach may not be in anyone's best interest. Am J Nurs. 2006;106(8):56–63. Bratslavsky G, Kogan BA. Long-term efficacy of desmopressin in the treatment of giggle incontinence. J Urol. 2003;170(4 Pt 2):1633–4. Lottmann HB, Alova I. Primary monosymptomatic nocturnal enuresis in children and adolescents. Int J Clin Pract Suppl. 2007;(155):8–16. Nevéus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children's Continence Society. J Urol. 2006;176(1):314–24. Additional Declarations No competing interests reported. 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Unlike stress urinary incontinence or other forms of bladder dysfunction, giggle incontinence involves total bladder evacuation during episodes of intense laughter, often leaving patients socially embarrassed and psychologically distressed (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFirst described systematically by Glahn in 1979 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), giggle incontinence predominantly affects children and adolescents, with most cases resolving spontaneously by late adolescence. The exact pathophysiology remains elusive, though proposed mechanisms include transient detrusor-sphincter dyssynergia, neurological factors affecting bladder control during emotional states, and potential genetic predisposition (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Epidemiological data on giggle incontinence are scarce, with most knowledge derived from isolated case reports and small case series, making prevalence estimates difficult (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe condition can significantly impact patients' quality of life, leading to social withdrawal, school absenteeism, and psychological distress (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Treatment approaches have been largely empirical, with variable success rates reported for anticholinergic medications (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), methylphenidate (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), and behavioral interventions (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBetween 2023 and 2025, we observed an unexpectedly high number of giggle incontinence cases in our urology practice in Toyserkan, a city in western Iran with a population of approximately 100,000. The concentration of cases, along with observed familial clustering, prompted us to systematically document and analyze this cohort. This case series aims to describe the clinical characteristics, treatment outcomes, and potential regional factors contributing to this apparent cluster of giggle incontinence cases.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy Design and Setting\u003c/h2\u003e\n\u003cp\u003eThis retrospective case series included all consecutive patients diagnosed with giggle incontinence at the Department of Urology, Toyserkan Hospital, Toyserkan, Iran, between January 2023 and August 2025. Toyserkan is a city in Hamedan Province, western Iran, with a population of approximately 100,000.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003ePatient Selection\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eInclusion Criteria:\u003c/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eComplete involuntary bladder emptying triggered exclusively by laughter\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAge\u0026thinsp;\u0026lt;\u0026thinsp;20 years at presentation\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAbsence of anatomical urinary tract abnormalities\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eNo evidence of neurological disease\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eComplete medical records available\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/div\u003e\n\u003ch3\u003eExclusion Criteria:\u003c/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eStress urinary incontinence or other forms of incontinence\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eDaytime urinary frequency without laughter trigger\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eNeurogenic bladder dysfunction\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAnatomical abnormalities of the urinary tract\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eMedical records were systematically reviewed for the following variables:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eDemographic data (age, gender)\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAge at symptom onset\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eSymptom duration before presentation\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eEpisode frequency and severity\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eFamily history of giggle incontinence or urinary disorders\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003ePhysical examination findings\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eDiagnostic test results (urinalysis, ultrasonography, urodynamic studies when performed)\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTreatment modalities employed\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTreatment outcomes and follow-up duration\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003eDiagnostic Criteria\u003c/h2\u003e\n\u003cp\u003eGiggle incontinence was diagnosed based on:\u003c/p\u003e\n1. Detailed history taking focusing on the temporal relationship between laughter and complete bladder emptying\n\u003cp\u003e2. Normal voiding pattern at all other times\u003c/p\u003e\n\u003cp\u003e3. Complete physical examination including neurological assessment\u003c/p\u003e\n\u003cp\u003e4. Laboratory investigations:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eComplete urinalysis and urine culture to exclude infection\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eBasic metabolic panel\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n5. Imaging studies:\u003cbr /\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eRenal and bladder ultrasonography to exclude anatomical abnormalities\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eUrodynamic studies when clinically indicated\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n6. Exclusion of other causes of urinary incontinence including stress incontinence, urge incontinence, and neurogenic bladder\u003c/div\u003e\n\u003ch3\u003eTreatment Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eTreatment Protocol\u003c/div\u003e\n\u003cp\u003eAll patients were initially managed with comprehensive behavioral modifications including:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eTimed voiding protocols with scheduled bladder emptying before situations likely to provoke laughter\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003ePelvic floor muscle training and exercises\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eFluid management strategies with avoidance of bladder irritants\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eCounseling regarding social situations and coping mechanisms\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003ePharmacological interventions were implemented when behavioral modifications proved insufficient:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAnticholinergic medication\u003c/strong\u003e: Tolterodine extended-release formulation\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eDosage: 1\u0026ndash;2 mg every 12 hours (twice daily)\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTreatment duration: Minimum 3 months to assess efficacy\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAll 20 patients received tolterodine as the primary anticholinergic agent\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll patients were followed for a minimum of 2 years to assess long-term outcomes and spontaneous resolution patterns.\u003c/p\u003e\n\u003ch3\u003eOutcome Assessment\u003c/h3\u003e\n\u003cp\u003eTreatment outcomes were classified as:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eComplete resolution\u003c/strong\u003e: No incontinence episodes for \u0026ge;\u0026thinsp;3 months\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003ePartial improvement\u003c/strong\u003e: \u0026ge;50% reduction in episode frequency\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eNo response\u003c/strong\u003e: \u0026lt;50% reduction in episodes or no change\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eDescriptive statistics were used to summarize patient characteristics and outcomes. Continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with range. Categorical variables are presented as frequencies and percentages.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eEthical Considerations\u003c/h2\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. As a retrospective review of medical records with anonymized data, formal ethics committee approval was waived according to institutional guidelines. Patient confidentiality was strictly maintained.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePatient Demographics\u003c/h2\u003e \u003cp\u003eTwenty patients were diagnosed with giggle incontinence during the study period. The cohort included patients aged 4 to 19 years (mean age: 7.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38 years; median: 7 years). The gender distribution showed a female predominance with 13 girls (65%) and 7 boys (35%). The age distribution showed clustering in the 6\u0026ndash;9 year age group (70% of cases).\u003c/p\u003e \u003cp\u003eThe mean symptom duration before presentation was 1.5 years (range: 1\u0026ndash;2 years). All patients reported severe symptoms with complete bladder emptying during laughter episodes, with variable frequency ranging from several times per week to daily occurrences.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eClinical Characteristics\u003c/h2\u003e \u003cp\u003eAll 20 patients presented with the pathognomonic feature of complete involuntary bladder emptying triggered exclusively by laughter. Between episodes, voiding patterns were entirely normal with no daytime frequency, nocturia, or urgency. Physical examinations were unremarkable in all cases. Urinalysis showed no abnormalities, and renal and bladder ultrasonography revealed normal anatomy in all patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eFamilial Clustering\u003c/h2\u003e \u003cp\u003eA notable finding was the observation of familial aggregation in 3 patients (15% of the cohort). One family presented with three affected siblings (ages [to be specified]), representing a striking familial clustering pattern. This familial pattern suggests a potential genetic component to the condition in this population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Outcomes\u003c/h2\u003e \u003cp\u003eAll patients initially underwent a trial of comprehensive behavioral modifications for a minimum of 3 months. Behavioral interventions, including timed voiding protocols, pelvic floor muscle training, and fluid management strategies, were poorly tolerated and demonstrated minimal clinical efficacy in reducing the frequency or severity of incontinence episodes. Patient adherence to behavioral protocols was suboptimal, likely due to the unpredictable nature of laughter-triggered episodes and the difficulty of implementing preventive strategies in social situations.\u003c/p\u003e \u003cp\u003eSubsequently, all 20 patients (100%) were treated with tolterodine extended-release formulation (1\u0026ndash;2 mg every 12 hours):\u003c/p\u003e \u003cp\u003eTreatment outcomes after a minimum 3-month trial of tolterodine therapy:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eComplete resolution\u003c/b\u003e: 3 patients (15%) - no incontinence episodes for \u0026ge;\u0026thinsp;3 months\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePartial improvement\u003c/b\u003e: 6 patients (30%) - \u0026ge;50% reduction in episode frequency\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eNo response\u003c/b\u003e: 11 patients (55%) - \u0026lt;50% reduction or no change in symptoms\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe majority of patients (55%) showed no significant improvement with tolterodine therapy, highlighting the treatment-resistant nature of giggle incontinence in this cohort. Among responders (n\u0026thinsp;=\u0026thinsp;9, 45%), improvement was typically observed within 4\u0026ndash;6 weeks of initiating therapy, though the degree of response varied considerably.\u003c/p\u003e \u003cp\u003eLong-term follow-up (minimum 2 years, range: 2-2.5 years) revealed that patients with initial complete or partial response generally maintained their improvement with continued medication. However, some non-responders showed spontaneous improvement over time without pharmacological intervention, consistent with the natural history of potential spontaneous resolution during adolescence. No alternative pharmacological interventions (such as methylphenidate or desmopressin) were systematically employed in this cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eRegional Prevalence\u003c/h2\u003e \u003cp\u003eWith 20 cases identified over a 2-year period in a population of 100,000, the observed prevalence in Toyserkan appears substantially elevated compared to rates reported in international literature. This concentration of cases within a geographically defined population suggests potential regional clustering. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e Patient No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSymptom Duration (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFamilial Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes (Sibling 1/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes (Sibling 2/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eComplete resolution\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eComplete resolution\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes (Sibling 3/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePartial improvement\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eComplete resolution\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBehavioral\u0026thinsp;+\u0026thinsp;Tolterodine 1-2mg q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo response\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case series represents one of the largest single-center cohorts of giggle incontinence reported in the literature and reveals several clinically significant findings. The concentration of 20 cases in a population of 100,000 over two years suggests a prevalence substantially higher than previously reported rates, raising important questions about regional, genetic, or environmental factors that may predispose certain populations to this condition.\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eRegional Clustering and Potential Mechanisms\u003c/h2\u003e \u003cp\u003eThe apparent regional clustering observed in Toyserkan may be attributed to several factors:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGenetic Predisposition\u003c/strong\u003e \u003cp\u003eThe observation of familial clustering in 15% of cases, including one family with three affected siblings, strongly suggests a genetic component. Toyserkan's relative geographic isolation may have resulted in a founder effect or increased prevalence of specific genetic variants predisposing to giggle incontinence. This hypothesis is supported by the known consanguinity rates in Iranian populations and the possibility of recessive inheritance patterns becoming more apparent in genetically homogeneous communities.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEnvironmental Factors\u003c/strong\u003e \u003cp\u003eLocal environmental conditions, dietary patterns, or cultural practices specific to the region may contribute to the observed clustering. Further investigation into potential environmental triggers or protective factors is warranted.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDiagnostic Awareness\u003c/strong\u003e \u003cp\u003eAs the only specialized urology center in the region, increased awareness and systematic documentation in our practice may have improved case identification. However, the absolute number of cases and familial clustering patterns suggest this is unlikely to fully explain the phenomenon.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eClinical Characteristics and Age Distribution\u003c/h2\u003e \u003cp\u003eThe concentration of cases in the 6\u0026ndash;9 year age range (70% of patients) aligns with previous literature suggesting peak incidence during early to middle childhood (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, the presence of one 19-year-old patient demonstrates that the condition can persist into late adolescence, contrary to the assumption of universal spontaneous resolution (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe universal presentation of complete bladder emptying during laughter episodes, with otherwise normal voiding patterns, confirms the distinct clinical phenotype of giggle incontinence and differentiates it from other forms of pediatric incontinence (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Resistance and Clinical Implications\u003c/h2\u003e \u003cp\u003eThe limited efficacy of tolterodine therapy in our cohort (complete resolution in only 15%, no response in 55%) is striking and may suggest that giggle incontinence in this population represents a distinct pathophysiological subtype. This treatment resistance pattern differs from some reports in the literature suggesting better responses to anticholinergics (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), though variable treatment outcomes have been consistently noted across studies (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe pathophysiology of giggle incontinence remains poorly understood. Proposed mechanisms include:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eNeurological dysregulation\u003c/b\u003e: Emotional responses during laughter may trigger abnormal neural signaling affecting bladder control (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eCataplexy-like phenomenon\u003c/b\u003e: Some authors have suggested similarities to narcolepsy-cataplexy, given the emotional trigger and complete loss of control (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eDetrusor-sphincter dyssynergia\u003c/b\u003e: Transient incoordination between detrusor contraction and sphincter relaxation during laughter (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGenetic factors\u003c/b\u003e: Our familial clustering data support inherited susceptibility\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eThe treatment resistance observed in our cohort may indicate that the underlying pathophysiology in this regional cluster involves mechanisms less responsive to anticholinergic blockade, potentially supporting a more neurologically-mediated process. The poor response to behavioral interventions further suggests that simple bladder management strategies are insufficient for this condition, which may require more targeted neurological or pharmacological approaches.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eFamilial Aggregation and Genetic Implications\u003c/h2\u003e \u003cp\u003eThe identification of familial clustering in 15% of cases, particularly the family with three affected siblings, provides compelling evidence for genetic predisposition. To our knowledge, such clear familial aggregation has been infrequently reported in the giggle incontinence literature. This finding suggests that genetic studies in this population may be particularly informative for identifying susceptibility genes.\u003c/p\u003e \u003cp\u003ePotential genetic mechanisms could include:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAutosomal dominant inheritance with variable penetrance\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAutosomal recessive inheritance (more likely given consanguinity patterns)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePolygenic inheritance with environmental modifiers\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eEpigenetic factors influenced by regional environmental conditions\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eComparison with International Literature\u003c/h2\u003e \u003cp\u003ePublished prevalence data for giggle incontinence are limited, with most estimates derived from small studies suggesting rates well below what we observed (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Our finding of 20 cases per 100,000 population over two years in the pediatric and adolescent age range appears substantially elevated, supporting the hypothesis of true regional clustering rather than ascertainment bias alone.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eStudy Limitations\u003c/h2\u003e \u003cp\u003eSeveral limitations must be acknowledged:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eRetrospective design\u003c/b\u003e: Data were collected from medical records, potentially limiting the completeness and standardization of clinical information.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSingle-center study\u003c/b\u003e: While this allowed for consistent diagnostic criteria and management protocols, referral patterns may have influenced case identification.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLimited follow-up\u003c/b\u003e: Long-term outcomes beyond the immediate treatment period were not consistently available for all patients.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLack of control group\u003c/b\u003e: Without systematic screening of the general population, true prevalence estimates remain uncertain.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMissing genetic analysis\u003c/b\u003e: Formal genetic testing was not performed, limiting our ability to identify specific genetic factors.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eIncomplete treatment data\u003c/b\u003e: Detailed medication dosing, duration, and systematic assessment of all treatment modalities were not uniformly documented.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eClinical and Research Implications\u003c/h2\u003e \u003cp\u003eThis case series has several important implications:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eIncreased awareness\u003c/b\u003e: Clinicians in other geographically distinct or genetically homogeneous populations should systematically document giggle incontinence cases to identify similar clusters.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGenetic investigation\u003c/b\u003e: The familial clustering observed warrants formal genetic studies, including whole-exome sequencing of affected families to identify susceptibility genes.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eAlternative treatment strategies\u003c/b\u003e: Given the treatment resistance to anticholinergics, investigation of alternative approaches including methylphenidate (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), biofeedback (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), or neuromodulation may be warranted.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eEpidemiological studies\u003c/b\u003e: Systematic population-based screening in the region could provide accurate prevalence estimates and identify additional cases.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eInternational collaboration\u003c/b\u003e: Establishing registries and collaborative research networks may help identify genetic and environmental risk factors through multi-center studies.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case series documents an apparent regional clustering of giggle incontinence in Toyserkan, Iran, with 20 cases identified over two years in a population of 100,000. The notable familial aggregation, treatment resistance to conventional anticholinergic therapy, and geographic concentration suggest potential genetic predisposition or environmental factors specific to this region. These findings highlight the need for systematic epidemiological investigation, genetic studies, and development of alternative treatment strategies for this understudied and often treatment-resistant condition. We encourage international colleagues to systematically document similar cases to advance understanding of giggle incontinence epidemiology and pathophysiology.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003e This study was approved by the Ethics Committee of Hamadan University of Medical Sciences (approval number: IR.UMSHA.REC.1400.284) Written informed consent to participate was obtained from the parents or legal guardians of all minor participants, and assent was obtained from participants capable of providing it, in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eNot applicable. This manuscript does not contain any individual person's identifying data, images, or clinical details that would compromise anonymity. All patient data have been anonymized and presented in aggregate form.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eAll sources of funding for the research paid by Farshad Banouei.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eFB analyzed and interpreted the patient all data, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlahn BE. Giggle incontinence (enuresis risoria). A study and an aetiological hypothesis. Br J Urol. 1979;51(5):363\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiddens JL, Bauer SB, Hallett M, Khoshbin S, Kelly MD, Darbey MM. The giggle incontinence syndrome: a scoping review. Pediatr Res. 2024;95(4):1021\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChung JM, Lee SD, Kang DI, Kwon DD, Kim KS, Kim SY, et al. An epidemiologic study of voiding dysfunction in children and adolescents: a population-based study. Neurourol Urodyn. 2010;29(8):1435\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeiss JP, Heesakkers JP, van Kerrebroeck PE, Klein BM, Nitti VW. Successful treatment of giggle incontinence with methylphenidate. J Urol. 1996;156(2 Pt 2):656\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerry AK. Helping children with nocturnal enuresis: the wait-and-see approach may not be in anyone's best interest. Am J Nurs. 2006;106(8):56\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBratslavsky G, Kogan BA. Long-term efficacy of desmopressin in the treatment of giggle incontinence. J Urol. 2003;170(4 Pt 2):1633\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLottmann HB, Alova I. Primary monosymptomatic nocturnal enuresis in children and adolescents. Int J Clin Pract Suppl. 2007;(155):8\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNev\u0026eacute;us T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children's Continence Society. J Urol. 2006;176(1):314\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Giggle incontinence, Enuresis risoria, Regional clustering, Familial aggregation, Pediatric urology","lastPublishedDoi":"10.21203/rs.3.rs-7842510/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7842510/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eGiggle incontinence (enuresis risoria) is a rare condition characterized by complete involuntary bladder emptying triggered by laughter. Limited epidemiological data exist regarding its prevalence and geographic distribution.To report an unexpectedly high incidence of giggle incontinence cases in Toyserkan, Iran, and describe the clinical characteristics, treatment responses, and potential familial clustering in this regional population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective case series of 20 consecutive patients diagnosed with giggle incontinence between 2023 and 2025 at Toyserkan Hospital. Clinical characteristics, family history, treatment modalities, and outcomes were systematically documented and analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty patients (age range: 4\u0026ndash;19 years, mean age: 7.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38 years) were diagnosed with giggle incontinence in a city with a population of 100,000. The mean symptom duration before presentation was 1.5 years (range: 1\u0026ndash;2 years). All patients presented with severe involuntary complete bladder emptying triggered exclusively by laughter. Diagnosis was confirmed through comprehensive history taking, physical examination, laboratory tests, and imaging studies. Familial clustering was observed in 15% of cases, including one family with three affected siblings. All patients initially received behavioral modifications, which showed poor adherence and minimal efficacy. Subsequently, all 20 patients were treated with tolterodine (1\u0026ndash;2 mg every 12 hours). Treatment outcomes showed complete resolution in 3 patients (15%), partial improvement in 6 patients (30%), and no response in 11 patients (55%) after minimum 3-month trial. Long-term follow-up (minimum 2 years) revealed sustained response in most initial responders, with some spontaneous improvement in non-responders over time. The prevalence rate of 20 cases per 100,000 population over two years appears substantially higher than previously reported international rates.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case series reveals a potential regional cluster of giggle incontinence in Toyserkan, Iran, with notable familial aggregation and treatment resistance. The findings suggest possible genetic predisposition or environmental factors specific to this geographic region, warranting further epidemiological investigation and genetic studies.\u003c/p\u003e","manuscriptTitle":"Regional Clustering of Giggle Incontinence in Toyserkan, Iran: A Case Series of 20 Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 12:17:41","doi":"10.21203/rs.3.rs-7842510/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-07T20:52:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T09:47:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70253827691255162468950350559599255990","date":"2026-02-27T19:52:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"206226259270084823497203897342737767680","date":"2026-02-25T15:27:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-25T08:28:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-30T19:41:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-14T21:29:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-13T16:43:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Urology","date":"2025-11-13T16:40:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc9c95bd-59dc-457a-a69b-563728418fbf","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T12:17:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 12:17:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7842510","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7842510","identity":"rs-7842510","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}