central nervous system changes following botulinumtoxina injection in the bladder

Conditions: Multiple Sclerosis; Lower Urinary Tract Symptoms; Neurogenic Bladder; Detrusor, Overactive; Urge Incontinence

Summary: the purpose of this prospective research study is to evaluate higher neural changes following intradetrusor injection of botulinum toxin-a (btx-a) in patients with multiple sclerosis (ms). concurrent urodynamic and functional magnetic resonance (fmri) data will be recorded pre- and post- intravesical injection of btx-a in patients with multiple sclerosis (ms) and neurogenic detrusor activity (ndo). other objectives are to evaluate the role of urinary biomarkers such as brain-derived neurotropic factor (bdnf) and nerve growth factor (ngf) associated with bladder overactivity and, to determine whether the common validated urgency questionnaires correlate with fmri findings and urinary biomarker concentration pre- and post- btx-a injection in patients with ms and ndo.

multiple sclerosis is a severe debilitating disease that affects patient's quality of life. up to 90% of patients with ms will develop lower urinary tract dysfunction within the first 18 years of the disease. lower urinary tract symptoms (luts) can range from urgency to urge urinary incontinence and/or hesitancy and incomplete bladder emptying. urgency, frequency, and neurogenic detrusor overactivity (ndo) are the most common urologic findings (34-99%) during diagnostic evaluations of patients with ms. even though anticholinergic or beta agonist drugs have limited effectiveness and adverse side effects, they are the first line pharmacotherapy for patients with ndo if behavioral modifications and pelvic floor physical therapy are unsuccessful. botulinum toxin-a (btx-a) intradetrusor injection is a highly effective treatment option for patients with ndo who are refractory to more conservative management. btx-a blocks the release of acetylcholine at the neuromuscular junction and leads to a temporary chemodenervation of the bladder (paralysis of the muscle). motor effects of btx-a on the bladder have been extensively studied and widely reported in the literature, and the us food and drug administration has approved btx-a for the treatment of detrusor overactivity in neurogenic and non-neurogenic patients. however, the sensory effects of btx-a injection correlating to central nervous system regional perception/localization of urgency, frequency, and urge incontinence in humans are not well known. over the past decades, functional mri (fmri) has been used to study the activation of supraspinal lower urinary tract control centers in healthy subjects during the storage and voiding phases. given these facts, the investigators are interested in evaluating the role of intradetrusor injection of btx-a in afferent response in patients with ms and ndo. high-resolution neuroimaging techniques will help investigators to further understand how ms affects the bladder-brain controls. this study will use fmri and task-related blood oxygen level dependent (bold) signal to evaluate patients with ms and ndo prior to, and 6-10 weeks after intradetrusor injection of btx-a with simultaneous urodynamic evaluation. clinical correlation between women with these chronic urologic problems and new discoveries at level of cns activity will give a better understanding of this disorder, leading to the development of more effective diagnostic and treatment modalities.

Eligibility criteria:
inclusion criteria: * patients with clinical diagnosis of neurogenic bladder. * history of any neurologic illness or injury (including but not limited to spinal cord injury, multiple sclerosis, spina bifida, parkinson's, major spine surgery). * 18 years or older. * female patients. exclusion criteria: * male * history of any incontinence surgery (sling, mmk, burch). * history of any lower urinary tract surgery or manipulation (urethral dilation). * positive urine pregnancy test at enrollment .

Keywords: neurogenic bladder, detrusor overactivity, botox, fmri