Analysis of the influence of the ADRB3 gene polymorphism and the detrusor-sphincter dyssynergy type in patients with neurogenic bladder in the course of multiple sclerosis on the effectiveness of botulinum toxin treatment - preliminary report.

Ciecwiez S1, Koziarska D2, Kotlega D3, Lewandowska K4, Ciechanowicz A4

Research Type

Clinical

Abstract Category

Overactive Bladder

Abstract 318
Open Discussion ePosters
Scientific Open Discussion Session 22
Friday 9th September 2022
13:30 - 13:35 (ePoster Station 2)
Exhibition Hall
Multiple Sclerosis Overactive Bladder Quality of Life (QoL) Voiding Dysfunction
1. Department of Gynaecology, Endocrinology and Gynaecologic Oncology, Pomeranian Medical University, Poland, 2. Department and Clinic of Neurology, Pomeranian Medical University, Poland, 3. Department of Applied and Clinical Physiology, Collegium Medicum, University of Zielona Gora, Poland, 4. Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Poland
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Poster

Abstract

Hypothesis / aims of study
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by disseminated lesions of demyelination and axonal loss leading to atrophy of the nervous tissue. In the course of the disease, there is a dysfunction of the central nervous system, resulting in motor and intellectual disability. The period of the disease falls in most cases, in the third decade of life, and the prospect of inevitable disability burdens the mentally ill and their relatives. One of the important non-sphincter symptoms is the lack of sphincter control: the neurogenic bladder. In the course of MS, the symptoms of overactive bladder may be present both in the states of periodic worsening - relapses, and permanently. Overactive bladder (OAB), as defined by ICS in 2002, is a multi-symptomatic disease that consists of urgency with or without urinary incontinence, usually with an increased frequency of daytime voiding and nocturia. When making a diagnosis, symptoms of mimicking diseases such as urinary tract infection, interstitial bladder inflammation, and bladder tumors and stones should be ruled out.
The disruption of the neural pathways connecting the ponsal micturition center to the sacral voiding center is usually the cause of detrusor-sphincter dyssynergy (DESD). Three main types of DESD are known. In the first type, the increase in detrusor pressure is accompanied by an increase in EMG activity. Type II DESD is characterized by occasional contractions of the external urethral sphincter during detrusor contraction. In type III DESD, the sphincter contracts in a characteristic cresendo-decresendo fashion, which causes a tubular obstruction throughout the detrusor contraction.
In line with the ICS guidelines, four lines of treatment of overactive bladder have been distinguished. Botulinum toxin is recommended as therapy for patients refractory to pharmacological treatment.
The mechanism of action of botulinum toxin is related to the ADRB 3 receptor, which has polymorphic variants.
The aim of the study was to assess the effectiveness of treatment of patients with neurogenic bladder in the course of multiple sclerosis with botulinum toxin depending on the type of detrusor-sphincter dyssynergy and on the polymorphism of the ADRB 3 gene.
Study design, materials and methods
35 patients with diagnosed neurogenic bladder in the course of multiple sclerosis were enrolled in the study on the basis of an interview, ICIQ-OAB, ICIQ-OABgol and ICIF-LUTSqol questionnaires. Each patient underwent urodynamic examination and a specific type of detrusor-sphincter dyssynergy. Each patient had a cheek swab taken to determine the ADRB 3 gene polymorphism. Each patient underwent the procedure of injecting botulinum toxin into the walls of the bladder in a hospital setting under general and intravenous anesthesia. After 3 months, each patient was re-interviewed using the ICIQ-OAB, ICIQ-OABgol and ICIF-LUTSqol questionnaires. Inclusion criteria for the study were no effect after pharmacological treatment, intolerance to pharmacological treatment, and age> 18 years of age. Exclusion criteria were prior intravesical administration of botulinum toxin, urinary tract infection, mixed urinary incontinence, and urogynecological surgeries. Only question 23 from the ICIQ-LUTSqal questionnaire to evaluate the effectiveness of botulinum toxin treatment was selected for the analysis.
Results
In 35 patients with neurogenic bladder in the course of MS, 33 patients were diagnosed with type 2 DESD and in 2 patients with type 1 DESD. No patient was diagnosed with type 3 DESD. Among 33 patients with type 2 DESD, 32 had the TT variant of the ADRB3 gene polymorphism (96.97%) and only 1 patient had the CT variant of the ADRB 3 gene polymorphism (3.03%). Among 2 patients with type 1 DESD, 1 patient had the TT variant of the ADRB3 gene polymorphism (50%) and 1 1 patient had the CT variant of the ADRB3 gene polymorphism (50%). In all patients, the quality of life improved significantly.
Interpretation of results
On the basis of the obtained results, a significant improvement in the quality of life was found in patients with neurogenic bladder in the course of multiple sclerosis after injecting the bladder walls with botulinum toxin 200 U. ADRB3. Most likely, the lack of a significant influence of the above analyzed relationships results from the small study group and taking into account only one variable from the quality of life survey (ICIQ-LUTSqol).
Concluding message
The procedure of injecting the bladder with botulinum toxin 200 U in patients with neurogenic bladder in the course of MS is very effective and significantly improves the quality of life. It seems that a much broader analysis is needed with more patients and variables to obtain more in-depth results, which is combined with an even greater understanding of the mechanism of action of botulinum toxin in these patients, and thus even more improvement in the quality of life and extension of the duration of the action of botulinum toxin in selected patients. female patients.
Disclosures
Funding Activity of the clinic Clinical Trial Yes Public Registry No RCT No Subjects Human Ethics Committee Local Ethics Committee - Independent Bioethics Commission for Research, Pomeranian Medical University in Szczecin Helsinki Yes Informed Consent Yes
16/07/2025 14:38:09